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  • Liposomes in the Treatment of Ovarian Cancer, and Liposomal Therapeutics: A Comprehensive Review

  • Photo Kiran Naik* Photo Vidya Thorat Photo P. N. Sable Photo Rupali Tiple

  • 1,2,3 SSP Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune, Maharashtra, India 411062

    4 SSSPM Shree Babasaheb Gharfalkar College of Pharmacy, Nachangaon, Pulgaon , Maharashtra, India 442302

Abstract

Ovarian cancer (OC) remains the deadliest of the gynecologic malignancies, largely because more than 70?% of patients present with advanced?stage disease and quickly acquire resistance to platinum?based chemotherapy. Liposomes spherical vesicles composed of one or more phospholipid bilayers were the first nanocarriers to translate from bench to bedside. By encapsulating cytotoxics or nucleic acids, liposomes can enhance pharmacokinetics, improve tumor deposition, and mitigate systemic toxicities. Pegylated liposomal doxorubicin (PLD) is now a backbone therapy for recurrent OC, and a new generation of trigger?responsive, ligand?targeted, and gene?loaded liposomes are poised to address persistent challenges such as intraperitoneal dissemination and genomic heterogeneity. This review summarizes the physicochemical foundations of liposome design, surveys current clinical and preclinical liposomal formulations in OC, highlights emerging strategies (stimuli?responsive, multi?drug, and immuno?activating systems), and discusses translational hurdles and future directions. Collectively, the field is moving toward precision nanomedicine in which liposomes function not only as drug ferries but also as programmable mini organs capable of sensing and modulating the tumor microenvironment.

Keywords

Ovarian cancer, Liposomes, Drug Delivery, Doxirubicin, Chemotherapy, Cisplatin

Introduction

Ovarian cancer accounts for approximately 313,?000 new diagnoses and 207,?000 deaths worldwide annually, making it the eighth leading cause of female cancer mortality [1]. Standard front?line management surgical cytoreduction plus platinum/taxane chemotherapy achieves high initial response rates, yet more than 80?% of patients relapse within two years [2]. Immunotherapies and molecularly targeted agents (e.g., PARP inhibitors) are now integral, but cumulative toxicities, dose?limiting myelosuppression, and poor intraperitoneal drug penetration still curtail durable control. Nanocarrier?mediated delivery, spearheaded by liposomes, emerged in the 1990s to re?engineer drug exposure profiles and exploit the enhanced permeability and retention (EPR) effect of tumors [3].

Liposomes consist of an aqueous core surrounded by lipid bilayer(s) that can incorporate hydrophilic and hydrophobic payloads. Stealth coatings (typically 2?kDa polyethylene glycol) extend circulation half?life from minutes to roughly 30?hours, while surface ligands such as folate or anti?EphA2 promote active targeting of OC cells [4]. To date, more than 15 liposomal drugs have received regulatory approval across indications, two of which PLD (Doxil/Caelyx) and liposomal irinotecan (Onivyde) have demonstrated survival benefit in solid tumors. OC, with its extensive peritoneal vascular fenestrations and high folate?receptor expression, is ideally suited for liposomal interventions [5].

This review first revisits liposome engineering principles before turning to OC biology. We then integrate clinical evidence for marketed and investigational liposomal agents, examine preclinical advances in gene and immune modulation, and critique translational challenges such as EPR heterogeneity and immune clearance. Finally, we outline future research priorities, including combinatorial nanomedicine and image?guided intraperitoneal delivery.

2.  Fundamentals of Liposome Technology:

2.1. Composition and Architecture:

Figure 1. Liposome structure showing the hydrophilic core and lipid bilayer.

A canonical liposome is built from phosphatidylcholine and cholesterol in a 55:45 mol%  ratio, affording a liquid ordered bilayer with low permeability to serum proteins. Manipulating lipid composition modulates rigidity, fusogenicity, and release kinetics [6]. High transition temperature lipids such as DSPC allow lysolipid thermosensitive liposomes that burst at 40-42?°C, enabling on-demand release during focused hyperthermia. Cationic lipids (e.g., DOTAP) electrostatically bind nucleic acids but provoke complement activation; ionizable lipids circumvent this by remaining neutral at physiologic pH and protonating in the acidic endosome [7].

2.2. Advantages of Liposomes:

  1. Biocompatibility and biodegradability: Liposomes are made from natural phospholipids and are generally non-toxic and well-tolerated.
  2. Targeted drug delivery: Liposomes can be surface-modified (e.g., with PEG or ligands) for active or passive targeting (e.g., tumors via the EPR effect).
  3. Improved drug stability: Protects encapsulated drugs from enzymatic degradation or environmental conditions.
  4. Reduced toxicity: Reduces exposure of non-target tissues, minimizing side effects (e.g., Doxil for doxorubicin).
  5. Versatility: Can carry both hydrophilic and hydrophobic drugs.

2.3. Disadvantages of Liposomes:

  1. High production cost: Preparation and scale-up require expensive materials and complex techniques.
  2. Short circulation half-life: Unmodified liposomes are rapidly cleared by the mononuclear phagocyte system (MPS).
  3. Stability issues: Liposomes may undergo oxidation, fusion, or leakage of the drug during storage.
  4. Low encapsulation efficiency: Especially for some hydrophilic drugs.
  5. Batch-to-batch variability: Difficult to maintain consistency in size, charge, and loading during large-scale production

2.4. Manufacturing Methods:

Thin?film hydration with extrusion remains ubiquitous for lab?scale batches, yet pharmaceutical?grade products rely on ethanol?injection or microfluidic mixing to ensure narrow polydispersity (<?0.1) and scalable throughput. Remote loading using a transmembrane (NH?)?SO? or pH gradient routinely achieves greater than 95?% doxorubicin entrapment at drug?to?lipid ratios of 0.2 (w/w) [8].

Manufacturing methods of liposomes vary based on the desired size, lamellarity (number of bilayers), drug encapsulation efficiency, and scalability. Below is a comprehensive overview of the commonly used liposome manufacturing techniques:

I. Thin Film Hydration (Bangham Method)

  • Principle: Formation of multilamellar vesicles (MLVs) by hydration of a dry lipid film.
  • Steps:
  • Dissolve lipids in an organic solvent (e.g., chloroform/methanol).
  • Evaporate solvent to form a thin lipid film on a flask wall.
  • Hydrate with aqueous buffer under agitation.
  • Sonication or extrusion can convert MLVs to small unilamellar vesicles (SUVs).
  • Advantages:
  • Simple and widely used.
  • Suitable for both hydrophilic and lipophilic drugs.
  • Disadvantages:
  • Low encapsulation efficiency for hydrophilic drugs.
  • Poor scalability[26].

II. Reverse Phase Evaporation Method (REV)

  • Principle: Formation of liposomes from water-in-oil emulsions followed by solvent evaporation.
  • Steps:
  • Dissolve lipids in an organic solvent.
  • Add aqueous drug solution to form W/O emulsion using sonication.
  • Remove solvent under reduced pressure to form liposomes.
  • Advantages:
  • High encapsulation efficiency of hydrophilic drugs.
  • Produces large unilamellar vesicles (LUVs).
  • Disadvantages:
  • Residual solvents may be toxic.
  • Difficult to scale-up[27].

III. Ethanol Injection Method

  • Principle: Lipids dissolved in ethanol are rapidly injected into an aqueous phase, forming liposomes.
  • Steps:
  • Dissolve lipids in ethanol.
  • Inject into aqueous buffer under constant stirring.
  • Ethanol is removed via dialysis or evaporation.
  • Advantages:
  • Simple and fast.
  • Suitable for small-scale preparations.
  • Disadvantages:
  • Low encapsulation efficiency.
  • Limited scalability[28].

IV. Microfluidics Method

  • Principle: Controlled mixing of lipid and aqueous streams in microchannels for uniform liposome formation.
  • Steps:
  • Lipid dissolved in solvent (e.g., ethanol).
  • Mixed with aqueous solution in microfluidic device.
  • Rapid mixing leads to self-assembly into liposomes.
  • Advantages:
  • High reproducibility and control over size.
  • Scalable and GMP-compliant.
  • Minimal solvent residue.
  • Disadvantages:
  • Requires specialized equipment[29].

V. Freeze–Thaw Method

  • Principle: Cycles of freezing and thawing disrupt and reform liposome membranes, enhancing drug encapsulation.
  • Steps:
  • Prepare MLVs using thin film hydration.
  • Subject liposomes to several freeze–thaw cycles.
  • Extrude or sonicate to obtain desired size.
  • Advantages:
  • Enhances encapsulation of hydrophilic drugs.
  • Produces stable vesicles.
  • Disadvantages:
  • Time-consuming.
  • Not ideal for thermolabile drugs[30].

VI. Detergent Removal Method

  • Principle: Liposomes form during the gradual removal of detergent from a lipid-detergent mixed micelle.
  • Steps:
  • Solubilize lipids in detergent solution.
  • Remove detergent by dialysis, gel filtration, or adsorption.
  • Advantages:
  • Produces uniform unilamellar vesicles.
  • Useful for reconstitution of membrane proteins.
  • Disadvantages:
  • Detergent removal can be slow.
  • Residual detergent may affect stability or safety[31].

Table No. 1 Comparison Table of Liposome Manufacturing Methods

Sr.No.

Method

Vesicle Type

Encapsulation Efficiency

Scalability

Complexity

1.

Thin Film Hydration

MLV, SUV

Low (hydrophilic drugs)

Low

Low

2.

Reverse Phase Evaporation

LUV

High

Moderate

Moderate

3.

Ethanol Injection

SUV

Low

Moderate

Low

4.

Microfluidics

SUV, LUV

Moderate–High

High

High

5.

Freeze–Thaw

MLV → LUV

Improved

Low

Moderate

6.

Detergent Removal

SUV

Moderate

Low–Moderate

High

2.5. Pharmacokinetics and Biodistribution:

Stealth liposomes evade opsonization and reduce hepatic capture, prolonging area under the curve and exploiting the leaky neovasculature of tumors (fenestrae 200–800?nm). However, EPR is heterogenous across patients and even within a single tumor [9]. Strategies to boost deposition include low?dose TNF?α, ultrasound?mediated microbubble disruption, and ligand?mediated endocytosis.

Liposomes, as nanoscale drug carriers, significantly alter the pharmacokinetics (PK) and biodistribution (BD) profiles of encapsulated therapeutics compared to their free forms. Their size, composition, surface characteristics, and route of administration influence their in vivo behavior, enhancing therapeutic efficacy and minimizing systemic toxicity.

2.5.1. Pharmacokinetics of Liposomes

Liposomes modify all four pillars of pharmacokinetics - absorption, distribution, metabolism, and excretion (ADME) to improve drug performance.

  1. Absorption and Circulation
  • Liposomes are predominantly administered intravenously, bypassing absorption barriers and enabling immediate systemic availability.
  • PEGylated liposomes, also known as "stealth" liposomes, evade the mononuclear phagocyte system (MPS), leading to prolonged plasma circulation time often several hours to days [4].
  1. Distribution
  • The distribution of liposomes is mainly confined to the vascular and interstitial spaces. Due to their size (typically 50–200 nm), liposomes do not diffuse freely across tight capillary junctions.
  • Accumulation in tissues occurs via the Enhanced Permeability and Retention (EPR) effect, especially in tumors and inflamed tissues [51].
  1. Metabolism
  • Liposomes are biologically metabolized by enzymes such as phospholipases, or taken up by liver and spleen macrophages, where they undergo lysosomal degradation [52].
  • The encapsulated drug may be released before, during, or after uptake depending on liposomal stability and composition.
  1. Excretion
  • Liposomal components are primarily eliminated via hepatic metabolism and biliary excretion.
  • Hydrophilic drugs may also be excreted renally after release from liposomes.

2.5.2. Factors Influencing Liposome Pharmacokinetics

Table No. 2 Factors Influencing Liposome Pharmacokinetics[53]

Factor

Effect on PK

Size

Larger liposomes (>200 nm) are cleared more rapidly.

Charge

Neutral or slightly negative charges favor longevity.

Surface Modification

PEGylation prolongs circulation and reduces RES uptake.

Lipid Composition

Saturated lipids and cholesterol enhance stability.

2.5.3. Biodistribution of Liposomes

  1. Passive Targeting (EPR Effect)

Tumors, due to defective vasculature and impaired lymphatic drainage, allow nanoscale liposomes to accumulate preferentially—a phenomenon called the EPR effect [51].

  1. Active Targeting

Surface modification with ligands such as antibodies, peptides, aptamers, or sugars enables receptor-mediated endocytosis, increasing specificity and uptake by target cells [54].

  1. Reticuloendothelial System (RES) Uptake

Unmodified liposomes are rapidly sequestered by macrophages in the liver, spleen, and lungs. PEGylation reduces this uptake, but some accumulation in these organs still occurs [55].

2.5.4. Organ Distribution Overview

Table No. 3 Organ Distribution Overview

Organ

Liposome Accumulation

(↑ High / ↓ Low)

Liver

↑ (especially Kupffer cell uptake)

Spleen

↑

Lung

↑ (in some formulations)

Tumor tissue

↑ (via EPR and active targeting)

Kidney

↓ (limited renal clearance)

Heart/Brain

↓ (blood-brain barrier limits entry)

2.5.5. Intracellular Fate

After reaching the target tissue, liposomes may be:

  • Endocytosed by cells (especially in active targeting).
  • Fused with the cell membrane (rare).
  • Degraded in lysosomes, releasing the drug into the cytoplasm or nucleus depending on drug properties [56].

2.5.6. Clinical Relevance

Liposomal drugs such as Doxil® (pegylated liposomal doxorubicin) and Ambisome® (liposomal amphotericin B) demonstrate:

  • Reduced cardiotoxicity.
  • Improved efficacy.
  • Altered biodistribution and enhanced accumulation in disease sites.

Their pharmacokinetic advantages result in higher area under the curve (AUC), lower peak plasma concentrations (Cmax), and prolonged half-life, especially compared to conventional free drugs [6].

2.6. Safety Profile:

PEGylation dramatically lowers infusion?related reactions but introduces accelerated blood clearance upon repeat dosing. Hand?foot syndrome and mucositis, while milder than the neutropenia and alopecia typical of free doxorubicin, remain dose?limiting for PLD. Novel hydrophilic coatings and intermittent dosing schedules mitigate hand?foot syndrome incidence to below 10?% [10].

Liposomes are among the most extensively studied nanocarriers for drug delivery, particularly in oncology, due to their biocompatibility, reduced systemic toxicity, and ability to encapsulate both hydrophilic and hydrophobic drugs. However, like any therapeutic system, they are not devoid of adverse effects and safety considerations.

2.6.1. Biocompatibility and Immunogenicity

Liposomes, particularly those composed of natural or synthetic phospholipids, exhibit excellent biocompatibility. Their similarity to biological membranes contributes to low immunogenicity. However, certain formulations can still provoke immune responses:

  • Complement activation-related pseudoallergy (CARPA): Some patients exhibit hypersensitivity reactions upon administration of liposomes, especially PEGylated liposomes like Doxil (PEGylated liposomal doxorubicin) [58]. This is due to activation of the complement system.
  • Anti-PEG antibodies: Repeated administration of PEGylated liposomes can induce formation of anti-PEG IgM antibodies, accelerating blood clearance of subsequent doses [62].

2.6.2. Toxicity

  • Reduced systemic toxicity: Liposomal encapsulation generally reduces toxicity by altering pharmacokinetics, enabling more targeted drug delivery. For example, PLD (Pegylated Liposomal Doxorubicin) reduces the cardiotoxicity seen with free doxorubicin [57].
  • Skin-related toxicities: A notable adverse effect of PLD is palmar-plantar erythrodysesthesia (PPE) or hand-foot syndrome, caused by accumulation in skin tissues due to the liposomes’ long circulation time [63].
  • Liver and spleen accumulation: Due to uptake by the mononuclear phagocyte system (MPS), liposomes often accumulate in the liver and spleen. While this is generally safe, in some patients with compromised hepatic function, it may cause hepatotoxicity [64].

2.6.3. Influence of Physicochemical Properties on Safety

  • Size and charge: Liposomes of smaller size (<100 nm) and near-neutral surface charge tend to evade rapid MPS clearance, prolonging circulation time but may also increase systemic exposure.
  • Surface modifications (e.g., PEGylation): Improve stability and half-life but can lead to immunogenicity upon repeated dosing.
  • Lipid composition: Natural lipids like phosphatidylcholine are less toxic than synthetic or charged lipids.

2.6.4. Safety in Special Populations

  • Pregnant and lactating women: Data is limited. Most liposomal drugs are contraindicated unless benefits outweigh risks.
  • Children and elderly: Safety profiles may differ due to metabolic variations; clinical studies are needed for dose adjustment.
  • Immunocompromised patients: Potential for reduced immune clearance of liposomes, but also reduced immunogenicity-related side effects.

2.6.5. Clinical Evidence

  • Doxil (PLD): Demonstrated a more favorable safety profile than conventional doxorubicin in ovarian cancer, Kaposi's sarcoma, and multiple myeloma. Cardiotoxicity rates are significantly reduced [65].
  • DaunoXome: Liposomal daunorubicin with reduced mucositis and myelosuppression compared to free daunorubicin [66].

2.6.6. Regulatory and Long-Term Safety

  • Liposomal formulations are generally well-regulated by agencies like the FDA and EMA.
  • Requirements include comprehensive safety, biodistribution, and stability data.
  • Long-term safety studies are limited, especially for newer designer liposomes (e.g., stimuli-responsive or ligand-targeted types), necessitating further investigation.

3.  Ovarian Cancer Biology and Treatment Landscape:

Figure 2. Ovarian Cancer Biology

Epithelial ovarian cancer (EOC) constitutes approximately 90?% of cases and is subdivided into high?grade serous, endometrioid, clear?cell, mucinous, and low?grade serous subtypes [2]. TP53 mutations dominate high?grade serous carcinogenesis, accompanied by homologous?recombination deficiency in about 50?% of tumors, rendering them sensitive to PARP inhibition. Peritoneal dissemination, ascites formation, and immune?suppressive macrophages characterize advanced disease.

First?line therapy comprises optimal debulking surgery plus carboplatin and paclitaxel, sometimes augmented by bevacizumab. Despite an 80–90?% objective response rate, median progression?free survival is roughly 18 months. Platinum?resistant relapse carries a median overall survival of 12 months, prompting exploration of non?cross?resistant agents such as PLD. The peritoneal?plasma barrier and dose?limiting myelosuppression often halt dose intensification; hence nanocarrier delivery to intensify intratumoral exposures while sparing marrow is compelling.

Unique features of OC that favor liposomal strategies include folate receptor?α overexpression on most serous tumors, large peritoneal surface area that promotes nanoparticle settling, and tumor ascites acting as a drug reservoir. In summary, OC pathobiology both necessitates and facilitates liposome?mediated interventions.

4. Liposomes Used in Ovarian Cancer:

Figure 3. Timeline depicting key liposomal formulations developed for ovarian cancer treatment.

Liposomes have revolutionized the field of drug delivery, offering promising therapeutic avenues particularly in oncology. In ovarian cancer (OC), where the disease is often diagnosed at an advanced stage with extensive peritoneal spread, liposomal technologies have found unique utility. The need for enhanced drug delivery platforms stems from challenges such as systemic toxicity of conventional chemotherapeutics, limited intraperitoneal drug penetration, chemoresistance, and immunosuppressive tumor microenvironments. Liposomes provide a means of delivering higher concentrations of therapeutic agents directly to tumor tissues, minimizing off-target effects and improving the therapeutic index.

The most well-established liposomal formulation in OC therapy is Pegylated Liposomal Doxorubicin (PLD), known by the brand names Doxil® and Caelyx®. The encapsulation of doxorubicin within PEGylated liposomes enhances its plasma half-life and improves its accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. Numerous clinical trials have demonstrated the efficacy of PLD in recurrent and platinum-resistant ovarian cancer, showing an objective response rate of 15–20% and a favorable toxicity profile characterized by reduced cardiotoxicity and alopecia [1,2]. PLD is often used in combination with carboplatin, with meta-analyses supporting its superiority over traditional paclitaxel–carboplatin regimens in prolonging progression-free survival [3].

Lipoplatin®, a liposomal formulation of cisplatin, addresses the critical limitation of nephrotoxicity associated with free cisplatin. Its lipid encapsulation reduces renal accumulation, enabling safer administration at effective doses. Phase II studies have demonstrated non-inferiority in clinical outcomes with a better renal safety profile [4]. Lipoplatin has shown synergy with paclitaxel and is being evaluated for use in platinum-sensitive and platinum-resistant cases alike.

LEP-ETU, a liposomal formulation of paclitaxel, is under development to reduce hypersensitivity reactions and eliminate the need for Cremophor EL, a solvent responsible for severe infusion reactions. LEP-ETU exhibits greater stability and sustained release kinetics, with enhanced bioavailability in the peritoneal cavity an ideal feature for OC management [5].

Folate-receptor-targeted liposomes exploit the overexpression of folate receptor-α (FR-α) in over 80% of epithelial OC cases. By conjugating folate to the liposome surface, drug payloads such as doxorubicin, paclitaxel, and PARP inhibitors are directed to tumor cells with high specificity. Preclinical studies have shown enhanced internalization and cytotoxicity, while clinical trials are assessing efficacy and safety [6,7]. Targeted liposomes improve drug accumulation in tumors, reduce systemic distribution, and demonstrate lower off-target effects.

Another advancement includes the use of immuno-liposomes, liposomes engineered to deliver immunotherapies such as anti-PD-1, anti-CTLA-4, and immune-activating cytokines like IL-2 or GM-CSF. These liposomes aim to modulate the tumor microenvironment, enhancing antigen presentation and overcoming immune evasion. In OC, where immunotherapy responses have historically been limited, this approach shows promise in reactivating anti-tumor immunity [8,9].

Gene therapy liposomes represent a novel strategy aimed at modulating genetic pathways involved in chemoresistance and tumor progression. Cationic liposomes have been employed to deliver tumor suppressor genes (e.g., p53, BRCA1/2), siRNA against drug resistance genes (e.g., MDR1), and CRISPR-Cas9 elements targeting oncogenic mutations. Several animal studies have demonstrated tumor regression, delayed recurrence, and increased sensitivity to platinum-based chemotherapy following gene delivery via liposomes [10,11]. Ionizable lipid nanoparticles provide superior transfection efficiency and reduced systemic toxicity compared to traditional cationic systems.

Furthermore, exosome-mimetic liposomes are an emerging class of hybrid nanocarriers that incorporate exosomal membrane proteins to enhance biocompatibility and tumor tropism. These vesicles mimic the natural targeting abilities of exosomes while leveraging the stability and drug-loading capacity of liposomes. Studies in OC models indicate increased peritoneal retention and effective delivery of paclitaxel and siRNA payloads to drug-resistant tumor cells [12].

Stimuli-responsive liposomes, designed to release their contents in response to environmental cues such as low pH, enzymatic activity, or elevated glutathione levels, are also under investigation. Given the acidic tumor microenvironment and the presence of reductive agents in the intracellular space, these liposomes provide controlled and site-specific release of therapeutic agents. Preclinical trials have confirmed their capacity to reduce systemic exposure and enhance tumor-specific cytotoxicity [13].

Moreover, multimodal liposomes incorporating imaging agents such as gadolinium for MRI or copper-64 for PET have been developed to enable real-time tracking of liposome biodistribution and therapeutic monitoring. Such theranostic systems could facilitate personalized dosing and improve response assessment in OC patients [14].

Sonodynamic and photodynamic liposomes (e.g., porphysomes) are another exciting innovation, offering the ability to generate cytotoxic reactive oxygen species upon ultrasound or light exposure. These platforms allow for externally controlled, spatially confined therapy and have shown promise in intraperitoneal OC models, where precision is key to avoid damaging healthy tissue [15].

Taken together, the liposomal systems used in ovarian cancer ranging from classic chemotherapeutic carriers to sophisticated gene and immune modulators represent a diverse and rapidly evolving toolkit. As understanding of tumor biology, nanomedicine, and immune-oncology deepens, these systems are likely to become increasingly customized, combinatorial, and intelligent, heralding a new era of precision medicine for ovarian cancer treatment.

5.  Liposomes in Cancer Therapy Beyond Ovarian Cancer:

5.1. Pegylated Liposomal Doxorubicin (Doxil/Caelyx):

Approved in 1995, PLD remains the archetype. By remote?loading doxorubicin into PEGylated vesicles (~100?nm), PLD achieves a plasma half?life of 55?hours and ten?fold higher tumor exposure compared with free drug [12].

Pegylated liposomal doxorubicin (PLD), marketed as Doxil® (US) and Caelyx® (EU/Canada), is a landmark nanomedicine formulation widely used in oncology beyond ovarian cancer. Encapsulation of doxorubicin in PEGylated liposomes extends its circulation half-life, enhances tumor accumulation via the enhanced permeability and retention (EPR) effect, and reduces cardiotoxicity a major dose-limiting toxicity of free doxorubicin.

      1. Clinical Applications Beyond Ovarian Cancer
  • Metastatic Breast Cancer (MBC)

PLD is approved as a monotherapy for patients with MBC, especially those with cardiac risk factors or who have failed prior anthracycline treatment. It is preferred due to its lower cardiotoxicity profile. In Phase III trials, PLD showed comparable efficacy to conventional doxorubicin with significantly reduced heart failure rates [65].

  • Multiple Myeloma

In combination with bortezomib, PLD improves progression-free survival in relapsed/refractory multiple myeloma. This combination enhances anti-myeloma activity without adding significant toxicity [86].

  • Kaposi’s Sarcoma (AIDS-related)

PLD remains a first-line treatment for AIDS-related Kaposi’s Sarcoma. Its efficacy, safety, and outpatient convenience have made it the standard of care since the late 1990s [87].

  • Endometrial and Other Gynecologic Cancers

PLD has been tested in advanced/recurrent endometrial cancers with modest activity. It is sometimes used off-label when platinum-based regimens fail [88].

  • Hepatocellular Carcinoma (HCC)

While not FDA-approved for HCC, PLD has been explored in Phase II studies due to its altered pharmacokinetics and safer hepatic profile [89].

      1. Advantages of PLD over Free Doxorubicin
  • Reduced Cardiotoxicity

PEGylation shields the liposome, avoiding rapid clearance and minimizing free drug exposure to the heart.

  • Improved Pharmacokinetics

PLD exhibits a circulation half-life of ~55 hours vs. ~20 minutes for free doxorubicin.

  • Tumor-Targeted Delivery

Exploits the EPR effect for better tumor uptake.

  • Reduced Myelosuppression and Alopecia

Less systemic exposure results in a milder side-effect profile.

      1. Limitations
  • Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia)

A unique dose-limiting side effect of PLD due to accumulation in skin capillaries.

  • Infusion Reactions

Though rare, PLD can cause hypersensitivity reactions requiring premedication.

  • High Cost

The formulation is significantly more expensive than generic doxorubicin.

5.2. Vyxeos (CPX?351):

Vyxeos encapsulates a synergistic 5:1 molar ratio of daunorubicin to cytarabine, demonstrating that liposomes can co?load fixed drug ratios unachievable by co?infusion. Vyxeos® (CPX?351) is a dual-drug liposomal formulation co-encapsulating daunorubicin and cytarabine in a fixed, synergistic molar ratio of 1:5. Approved by the FDA in 2017 and subsequently by the EMA, Vyxeos represents a major advancement in liposomal nanomedicine, specifically for the treatment of high-risk acute myeloid leukemia (AML) a malignancy that has historically posed treatment challenges due to poor prognosis and the toxicity of intensive chemotherapy.

5.2.1. Mechanism and Design Innovation

Vyxeos uses a bilamellar liposomal vesicle system to co-encapsulate daunorubicin and cytarabine at a fixed 1:5 molar ratio, enabling:

  • Co-delivery to leukemic cells
  • Sustained and controlled release
  • Improved pharmacokinetics
  • Reduced off-target toxicity

This fixed ratio was determined through preclinical synergy screening, maximizing anti-leukemic activity while reducing drug antagonism between the two agents [90].

5.2.2. Indications Beyond Ovarian Cancer

Vyxeos has clinical application primarily in hematologic malignancies:

1. Therapy-Related AML (t?AML)

  • Arises as a secondary cancer following chemotherapy or radiation.
  • Patients often show poor response to standard 7+3 therapy.
  • Vyxeos is approved for newly diagnosed t-AML due to superior efficacy.

2. AML with Myelodysplasia-Related Changes (AML?MRC)

  • Includes cases with prior myelodysplastic syndromes (MDS) or cytogenetic abnormalities.
  • Vyxeos improves survival and transplant eligibility in these patients.

3. Potential Expansion (Investigational)

  • Clinical trials are investigating Vyxeos in secondary AML, relapsed/refractory AML, and combinations with venetoclax [92].

5.2.3. Clinical Efficacy

Table No. 4: A pivotal Phase III trial compared Vyxeos to conventional 7+3 chemotherapy in older adults with newly diagnosed high-risk AML [91]

Outcome

Vyxeos

7+3 Standard Therapy

Median Overall Survival

9.56 months

5.95 months

Complete Remission (CR)

37.3%

25.6%

60-day Mortality

13.7%

21.2%

Time to Transplant

Shorter

Longer

These findings led to its regulatory approvals and established Vyxeos as standard of care in high-risk AML subtypes.

5.2.4. Advantages Over Conventional Chemotherapy

  • Maintains synergistic drug ratio in vivo
  • Preferential accumulation in bone marrow
  • Lower early mortality
  • Improved transplant bridging
  • Enhanced pharmacokinetics and biodistribution

5.2.5. Limitations and Toxicities

  • Myelosuppression: Longer neutropenia and thrombocytopenia
  • Infection Risk: Requires supportive care and antimicrobial prophylaxis
  • Cost: Significantly higher than standard therapy
  • Subtype-Specific Benefit: Not effective in all AML types

5.3. Onivyde (Liposomal Irinotecan):

Onivyde’s sucrose?octasulfate gradient stabilizes irinotecan in its active lactone form, extending half?life and reducing gastrointestinal toxicity in pancreatic cancer. Onivyde® (also known as nal-IRI or liposomal irinotecan) is a liposomal formulation of the topoisomerase I inhibitor irinotecan, designed to improve drug delivery and pharmacokinetics in solid tumors, particularly pancreatic cancer. It was approved by the FDA in 2015 for use in combination therapy for metastatic pancreatic adenocarcinoma following gemcitabine-based treatment.

5.3.1. Mechanism and Liposomal Design

Onivyde encapsulates irinotecan in a PEGylated liposomal carrier, which:

  • Prolongs systemic circulation of the drug.
  • Enables enhanced permeability and retention (EPR) effect in tumors.
  • Provides a controlled and sustained release of active metabolite SN-38.
  • Improves tumor targeting and reduces peak plasma levels, minimizing gastrointestinal and hematologic toxicities.

PEGylation also contributes to the stability of the liposome and reduces opsonization and clearance by the mononuclear phagocyte system (MPS) [73].

5.3.2. Approved Clinical Indication

Metastatic Pancreatic Cancer: Onivyde is FDA-approved for use in combination with fluorouracil (5-FU) and leucovorin in patients with metastatic pancreatic cancer who have progressed on gemcitabine-based therapy. Pancreatic cancer typically has a poor prognosis, and Onivyde has demonstrated a survival benefit in this difficult-to-treat population.

5.3.3. Clinical Efficacy (NAPOLI-1 Trial)

In the Phase III NAPOLI-1 trial, patients with metastatic pancreatic cancer previously treated with gemcitabine were randomized to receive either:

  • Onivyde + 5-FU/leucovorin
  • 5-FU/leucovorin alone

Table No. 5: Key outcomes of Clinical Efficacy (NAPOLI-1 Trial) [93]

Outcome

Onivyde Combo

5-FU/Leucovorin Alone

Median Overall Survival

6.1 months

4.2 months

Progression-Free Survival

3.1 months

1.5 months

Objective Response Rate

16%

1%

These results led to regulatory approval and support its use as second-line therapy in pancreatic cancer.

5.3.4. Potential Beyond Pancreatic Cancer (Investigational)

Although Onivyde is currently approved for pancreatic cancer, clinical trials have investigated or are ongoing in:

  • Colorectal cancer
  • Gastric cancer
  • Glioblastoma
  • Small cell lung cancer (SCLC)

Liposomal irinotecan demonstrates enhanced intratumoral SN-38 levels in several tumor types, suggesting broader applicability [94].

5.3.5. Advantages Over Conventional Irinotecan

  • Higher tumor accumulation of SN-38
  • Reduced peak-related systemic toxicity
  • Prolonged exposure and sustained antitumor effect
  • Better tolerated when combined with 5-FU/leucovorin

5.3.6. Limitations and Toxicity

  • Common adverse effects: Diarrhea, neutropenia, fatigue
  • Myelosuppression risk, especially in elderly or frail patients
  • Pharmacogenetic considerations: UGT1A1*28 polymorphism may increase SN-38 toxicity
  • High cost and availability may limit widespread use

6.  Clinically Approved and Investigational Liposomal Therapies in Ovarian Cancer:

6.1. Pegylated Liposomal Doxorubicin (PLD):

A 2024 meta?analysis of seven randomized trials (n?=?3?812) demonstrated that PLD?carboplatin significantly prolonged progression?free survival versus paclitaxel?carboplatin (hazard ratio 0.88) [13]. In platinum?resistant disease, PLD monotherapy yields an objective response rate of around 20?%.

Pegylated Liposomal Doxorubicin (PLD)

Pegylated Liposomal Doxorubicin (PLD), commercially known as Doxil® (US) or Caelyx® (EU), is a landmark in nanomedicine and a first-line liposomal chemotherapeutic agent approved for the treatment of platinum-resistant ovarian cancer. It represents one of the most clinically validated liposomal formulations in oncology.

  1. Formulation and Mechanism
  1. PLD is composed of:
  • Doxorubicin: An anthracycline antibiotic with cytotoxic activity via DNA intercalation, topoisomerase II inhibition, and generation of free radicals.
  • Liposome: A stealth (PEGylated) liposomal carrier made from hydrogenated soy phosphatidylcholine (HSPC), cholesterol, and methoxy-polyethylene glycol distearoylphosphatidylethanolamine (mPEG-DSPE).
  1. PEGylation allows:
  • Prolonged circulation half-life (up to 55 hours),
  • Reduced recognition and clearance by the mononuclear phagocyte system (MPS),
  • Enhanced Permeability and Retention (EPR) effect, leading to passive tumor targeting.
  1. Clinical Indications

PLD is approved for:

  • Recurrent platinum-resistant ovarian cancer, particularly after failure of first-line platinum-based chemotherapy.
  • Also indicated in AIDS-related Kaposi’s sarcoma and multiple myeloma (in combination with bortezomib).
  1. Efficacy in Ovarian Cancer

Numerous clinical trials have demonstrated the efficacy and safety of PLD in ovarian cancer.

  • Study Example: A phase III trial comparing PLD to topotecan in patients with platinum-refractory ovarian cancer showed:
  • Comparable overall survival (OS): PLD (60 mg/m² q28d) had OS of ~60 weeks.
  • Fewer grade 4 hematological toxicities, and reduced alopecia compared to topotecan [6].
  • In platinum-sensitive recurrence, PLD combined with carboplatin showed improved progression-free survival (PFS) over carboplatin alone.
  1. Advantages Over Free Doxorubicin

Table No. 6: Advantages of PLD Over Free Doxorubicin

Feature

Free Doxorubicin

PLD

Circulation time

Short

Prolonged (PEGylation)

Cardiotoxicity

High

Reduced

Tumor accumulation

Non-specific

Enhanced (via EPR effect)

Alopecia & mucositis

Common

Less frequent

Dosing frequency

More frequent

Once every 4 weeks
  1. Toxicity and Safety Profile
  • PLD reduces many traditional anthracycline-related toxicities, notably cardiotoxicity, due to lower peak plasma levels. However, notable adverse effects include:
  • Palmar-plantar erythrodysesthesia (PPE) or hand-foot syndrome
  • Stomatitis and mucositis
  • Myelosuppression (though less severe than topotecan)
  • Infusion reactions (rare, often preventable with premedication)
  • Long-term use does not typically result in cumulative cardiotoxicity, making it safer for prolonged administration in elderly or cardiac-risk patients [67].
  1. Formulation Challenges and Stability
  • Liposomes must remain stable in circulation but release the drug once inside the tumor.
  • PLD’s formulation uses a remote loading technique with an ammonium sulfate gradient to entrap doxorubicin effectively inside the aqueous core [68].
  1. Recent Developments and Research
  • PLD + anti-angiogenic agents: Combinations with bevacizumab or VEGF inhibitors are under investigation to enhance tumor vascular targeting.
  • PLD + PARP inhibitors: Studies suggest synergistic effects with olaparib or niraparib in BRCA-mutated ovarian cancer.
  • Novel PEGylation and stimuli-responsive formulations are being researched to reduce immunogenicity (CARPA) and improve tumor-specific drug release.
  1. Future Perspectives

While PLD has improved outcomes in ovarian cancer, resistance and limited penetration in poorly vascularized tumor areas remain challenges. Future iterations include:

  • Ligand-targeted liposomes (e.g., folate-receptor targeted),
  • Thermosensitive liposomes for triggered release,
  • Multimodal liposomes for combined therapy and imaging.

6.2. Lipoplatin:

Lipoplatin incorporates cisplatin into 110?nm vesicles to reduce nephrotoxicity. A phase?II trial reported grade 3?4 nephrotoxicity in none of the lipoplatin?treated patients versus 14?% with free cisplatin [14]. Lipoplatin is a liposomal encapsulation of the widely used chemotherapeutic agent cisplatin, developed to improve the therapeutic index of the drug by reducing systemic toxicity especially nephrotoxicity and enhancing tumor accumulation via the enhanced permeability and retention (EPR) effect [69,70].

6.2.1. Composition and Structure

Lipoplatin consists of cisplatin encapsulated in a liposome made from dipalmitoyl phosphatidyl glycerol (DPPG), soy phosphatidylcholine (SPC), cholesterol, and methoxy-polyethylene glycol-distearoylphosphatidylethanolamine (mPEG-DSPE). These components form a PEGylated liposome, which prolongs circulation time in the bloodstream and facilitates better tumor targeting [69,71].

6.2.2. Mechanism of Action

Lipoplatin acts via:

  • Passive targeting to tumors through the EPR effect.
  • Fusion with tumor cell membranes due to the lipid composition, enabling direct intracellular delivery of cisplatin.
  • Induction of apoptosis through DNA cross-linking and inhibition of DNA replication, similar to conventional cisplatin [69,70].

6.2.3. Preclinical and Clinical Investigations in Ovarian Cancer

Preclinical models have demonstrated increased accumulation of Lipoplatin in tumor tissues compared to free cisplatin [70,71]. Phase I/II trials have shown favorable safety profiles, particularly reduced renal and gastrointestinal toxicity [69]. In ovarian cancer, Lipoplatin has been explored both as a monotherapy and in combination with other agents like paclitaxel [72].

One clinical study found that the combination of Lipoplatin with paclitaxel yielded similar efficacy to standard cisplatin-paclitaxel regimens but with significantly lower nephrotoxicity and better patient tolerability [72].

6.2.4. Advantages over Conventional Cisplatin

  • Reduced nephrotoxicity, ototoxicity, and neurotoxicity [69,70].
  • Better patient compliance due to reduced side effects.
  • Enhanced delivery to tumor tissues due to liposomal encapsulation and PEGylation [70,71].

6.2.5. Limitations and Challenges

  • Still under investigation for FDA and EMA approval [69].
  • Cost of liposomal formulation is higher than free cisplatin.
  • Limited large-scale trials in ovarian cancer compared to other cancers like non-small cell lung cancer (NSCLC) [72].

6.2.6. Current Status

Lipoplatin has shown promising results in Phase II and III trials in various cancers (notably NSCLC), and though not yet widely approved for ovarian cancer, it remains an active area of research for platinum-resistant and recurrent disease cases [69,72].

6.3. OSI?211 (Liposomal Lurtotecan):

Early?phase trials showed modest response rates; modern ionizable lipid formulations are under re?evaluation. OSI?211, also known as Liposomal Lurtotecan, is an investigational liposomal formulation of lurtotecan, a water-insoluble camptothecin analogue and a topoisomerase-I inhibitor. Developed to address the challenges of drug solubility, toxicity, and limited efficacy of conventional camptothecins, OSI?211 has been explored as a potential therapy for platinum-resistant ovarian cancer.

6.3.1. Formulation and Design Rationale

Lurtotecan, the active agent, is encapsulated within a sterically stabilized liposome that contains:

  • Hydrogenated soy phosphatidylcholine (HSPC)
  • Cholesterol
  • PEGylated lipids (e.g., mPEG-DSPE)

This composition enhances the drug's pharmacokinetics, extends its plasma half-life, and enables passive tumor targeting via the enhanced permeability and retention (EPR) effect [73,74].

6.3.2. Mechanism of Action

Lurtotecan inhibits DNA topoisomerase I, an enzyme critical for DNA replication and transcription. By stabilizing the enzyme-DNA cleavable complex, it causes DNA strand breaks and induces cell death in rapidly dividing tumor cells [74].

The liposomal delivery system:

  • Shields the drug from rapid degradation.
  • Improves tumor accumulation.
  • Reduces off-target toxicity.

6.3.3. Clinical Investigation in Ovarian Cancer

In Phase II clinical trials, OSI?211 was administered intravenously to patients with platinum- and paclitaxel-resistant ovarian cancer. The studies reported:

  • Modest antitumor activity with partial response rates.
  • Median progression-free survival of approximately 2.4 months.
  • A more tolerable safety profile compared to conventional topoisomerase inhibitors [75].

Despite encouraging pharmacokinetics and safety, the efficacy results were not sufficient to support further development for ovarian cancer, and development was discontinued [75,76].

6.3.4. Advantages of OSI?211

  • Improved solubility of lurtotecan.
  • Reduced systemic toxicity.
  • Prolonged circulation time and enhanced tumor targeting.
  • Lower hematological and gastrointestinal toxicities compared to free lurtotecan [74,75].

6.3.5. Limitations

  • Modest response rates in heavily pretreated patients.
  • Lack of significant survival benefit over existing therapies.
  • Termination of development due to limited commercial viability [76].

6.3.6. Current Status

While OSI?211 is not approved and has been discontinued in ovarian cancer trials, it remains an important example of how liposomal encapsulation can enhance the delivery of otherwise challenging chemotherapeutic agents.

6.4. Combination Liposomes:

Folate?receptor?targeted liposomes co?encapsulating niraparib and doxorubicin achieved synergistic cytotoxicity and 85?% tumor regression in orthotopic models [15]. A first?in?human dose?escalation study began in 2024.

Combination liposomes are an advanced class of liposomal drug delivery systems engineered to co-encapsulate two or more therapeutic agents within a single nanocarrier. These systems aim to enhance synergistic anticancer effects, optimize drug ratios, and reduce systemic toxicity, particularly for multidrug-resistant and recurrent ovarian cancer.

6.4.1. Rationale for Combination Liposomal Therapy

Ovarian cancer frequently requires combination chemotherapy due to:

  • Intrinsic or acquired resistance to platinum-based agents.
  • Need to target multiple cancer pathways simultaneously.

Traditional combination regimens often suffer from inconsistent pharmacokinetics and differential toxicity of the co-administered drugs. Liposomal co-delivery offers a solution by synchronizing the delivery and biodistribution of multiple drugs [6,77].

6.4.2. Design and Mechanism

Combination liposomes are typically constructed using:

  • Co-loading strategies (e.g., passive loading, active loading with pH or ion gradients).
  • Fixed synergistic drug ratios, optimized through preclinical modeling (e.g., 1:1 or 5:1 molar ratios).
  • Stabilizing lipids such as DSPC, cholesterol, and PEGylated lipids to extend circulation time.

Once delivered to the tumor site via the enhanced permeability and retention (EPR) effect, the liposome releases both drugs in a controlled fashion to maintain the synergistic ratio at the cellular level [77,73].

6.4.3. Key Examples in Ovarian Cancer Research

  • Cisplatin + Doxorubicin Co-loaded Liposomes
  • Aim: Combine DNA cross-linking (cisplatin) with topoisomerase II inhibition (doxorubicin).
  • Result: Preclinical studies show enhanced apoptosis and reduced tumor burden in xenograft models [73].
  • Paclitaxel + Curcumin Liposomes
  • Aim: Combine microtubule inhibition with anti-inflammatory and anti-proliferative effects of curcumin.
  • Status: Under preclinical investigation for improved bioavailability and decreased resistance [78].
  • 5-FU + Irinotecan Liposomes (experimental)
  • Developed for colorectal cancer, but the model is inspiring ovarian cancer researchers to explore dual-action liposomes [79].

6.4.4. Advantages Over Single-Agent Liposomes

  • Synergistic antitumor effects from dual-drug action.
  • Improved pharmacokinetics and biodistribution of both agents.
  • Reduced multidrug resistance (MDR) by simultaneously targeting multiple mechanisms.
  • Lower cumulative toxicity compared to sequential administration.

6.4.5. Challenges and Limitations

  • Stability issues during co-encapsulation.
  • Difficulty maintaining the optimal synergistic ratio in vivo.
  • Complex regulatory approval pathways for multi-drug formulations.
  • Limited clinical data in ovarian cancer beyond preclinical stages [77,78].

6.4.6. Current Status and Future Prospects

Although combination liposomes have not yet received clinical approval for ovarian cancer, several formulations are in preclinical and early-phase trials. Their ability to address drug resistance and improve response rates makes them a promising direction in next-generation nanomedicine for ovarian cancer therapy.

6.5. TTFields?Compatible Liposomes:

Tumor?Treating Fields intensify membrane permeability, enhancing liposome uptake. Interim analysis of the INNOVATE?3 study suggests a potential survival benefit [16].

6.5.1. Tumor Treating Fields (TTFields) are an emerging, non-invasive cancer therapy that employs low-intensity, intermediate-frequency alternating electric fields to disrupt cancer cell division. In ovarian cancer, TTFields have shown potential when combined with conventional chemotherapy, particularly liposomal drug delivery systems, to enhance therapeutic outcomes while minimizing systemic toxicity [80].

6.5.2. TTFields-compatible liposomes are designed to retain their stability and function under the influence of alternating electric fields. These nanocarriers offer a dual approach leveraging the cytotoxic effects of both the encapsulated chemotherapeutic agents and the mitosis-disrupting action of TTFields [81]. Preclinical studies have demonstrated that TTFields can increase the permeability of cancer cell membranes, thereby enhancing the uptake of liposomes and improving drug delivery efficiency [82].

In addition, TTFields may facilitate localized and enhanced drug release from liposomes due to mechanical stress and changes in membrane dynamics. This results in increased intracellular drug concentration and greater cancer cell apoptosis [83].

6.5.3. Design of TTFields-Compatible Liposomes

To ensure effective co-delivery with TTFields, liposomes must meet certain structural criteria:

  • High structural stability under oscillating electric fields to prevent premature drug leakage.
  • Optimal size (~100 nm) to ensure enhanced permeability and retention (EPR) effect in tumors [6].
  • Surface PEGylation to prevent aggregation and prolong systemic circulation [4].
  • Neutral or negative surface charge, which has been found to improve electric field compatibility and minimize interactions that could destabilize the liposomes [84].

6.5.4. Investigational Use in Ovarian Cancer

Although TTFields-compatible liposomes are still in the investigational phase for ovarian cancer, combination therapies using pegylated liposomal doxorubicin (PLD) and TTFields have shown synergistic effects in both in vitro and in vivo models. These studies indicate higher drug accumulation at tumor sites and significantly greater tumor growth inhibition than either therapy alone [85].

This combination strategy holds promise for overcoming drug resistance in ovarian cancer, especially in recurrent or platinum-resistant cases. The integration of bioelectronic TTFields with nanotechnology-based delivery systems represents a novel therapeutic frontier.

7.  Preclinical Advances: Gene, RNA and Immune Modulation:

7.1. Gene Therapy Vectors

A 2023 systematic review of murine studies confirmed that cationic liposome?mediated gene delivery reduced mean tumor weight by 63?% and extended median survival by 25 days [17].

7.2. microRNA?Loaded Liposomes

microRNA?7 lipoplexes target EGFR and impair spheroid formation, while multiplex loading of miR?200c and miR?199a?3p is being explored to tackle epithelial–mesenchymal transition and angiogenesis [18].

7.3. Immuno?Liposomes and Oncolytic Viruses

Cationic liposomes formulated with DOTAP/DOPE facilitate reovirus entry, enhancing ovarian cancer cell kill in vitro by three?fold [19]. CD47?blocking immuno?liposomes improve phagocytic clearance of cancer spheroids.

7.4. Exosome?Mimetic Liposomes

Hybrid exosome?liposome nanovesicles combine innate tropism with scalable production, doubling peritoneal retention and reversing paclitaxel resistance in SKOV3?TR cells [20].

8.  Emerging Designer Liposomes:

8.1. Stimuli?Responsive Platforms

Endogenous stimuli such as acidic pH and elevated glutathione trigger selective payload release. A 2025 review catalogued more than 80 pH?sensitive systems [21].

Stimuli-responsive liposomes also called smart or triggered liposomes are advanced nanocarriers engineered to release their therapeutic payload in response to specific external or internal stimuli. These designer systems aim to enhance target specificity, minimize off-target toxicity, and overcome biological barriers, especially in solid tumours such as ovarian cancer.

8.1.1. Types of Stimuli and Mechanisms

a) pH-Responsive Liposomes

  • Mechanism: Exploit the acidic environment of tumour tissues (pH ~6.5) or intracellular compartments (endosomes/lysosomes, pH 5–6).
  • Design: Include pH-sensitive lipids (e.g., DOPE) or acid-labile linkers (e.g., hydrazone bonds).
  • Applications: Enhanced drug release in acidic tumour microenvironment (TME) or intracellular compartments [32].

b) Temperature-Responsive Liposomes

  • Mechanism: Release drugs when exposed to hyperthermia (~40–42°C), often achieved through localized heating.
  • Design: Use thermosensitive lipids like dipalmitoyl phosphatidylcholine (DPPC) that become more permeable at elevated temperatures.
  • Applications: Combine with focused ultrasound or microwave therapy to trigger site-specific release [33].

c) Enzyme-Responsive Liposomes

  • Mechanism: Trigger drug release in the presence of tumour-associated enzymes like matrix metalloproteinases (MMPs), phospholipases, or proteases.
  • Design: Incorporate enzyme-cleavable peptides or phospholipids as part of the liposomal structure.
  • Applications: Highly specific for metastatic or inflamed tissues [34].

d) Redox-Responsive Liposomes

  • Mechanism: Use the elevated levels of glutathione (GSH) in the cytosol or tumour cells to trigger disulfide bond cleavage.
  • Design: Disulfide-linked lipids or polymers destabilize in reductive environments, promoting drug release.
  • Applications: Targeting intracellular compartments or drug-resistant cancer cells [35].

e) Light-Responsive Liposomes

  • Mechanism: Use light (usually UV, visible, or NIR) to disrupt the liposomal membrane or activate photolabile groups.
  • Design: Include photosensitizers or light-cleavable lipids (e.g., azobenzene, o-nitro benzyl).
  • Applications: Ideal for surface or accessible tumours; enables precise spatial control [36].
      1. Advantages of Stimuli-Responsive Liposomes
  • Controlled and site-specific drug release
  • Reduced systemic toxicity
  • Enhanced intracellular uptake
  • Synergistic potential with imaging or hyperthermia
      1. Limitations
  • Complexity in formulation and scalability
  • Regulatory hurdles due to multifunctionality
  • Sensitivity to stimulus parameters (e.g., depth, uniformity)

8.2. Ligand?Targeted Approaches:

Beyond folate receptors, transferrin, integrin αvβ3, and EphA2 antibodies furnish targeting moieties, substantially increasing tumoral uptake without raising hepatic burden.

Ligand-targeted liposomes represent a powerful strategy in the design of “smart” or designer liposomes, aiming for active targeting of specific cell types especially cancer cells by using ligands that bind to overexpressed receptors on the target cell surface. This enhances cellular uptake, minimizes off-target effects, and improves therapeutic efficacy.

8.2.1. Mechanism of Action

  • Liposomes are surface-modified with ligands such as antibodies, peptides, aptamers, or small molecules.
  • These ligands recognize and bind to specific cell surface receptors (e.g., folate receptor, HER2, integrins).
  • After binding, liposomes are internalized via receptor-mediated endocytosis, enabling intracellular drug delivery.

8.2.2. Common Ligands Used

a. Monoclonal Antibodies (Immunoliposomes)

  • Example: Anti-HER2, Anti-EGFR
  • Used in targeting breast, ovarian, and lung cancers.
  • Antibody fragments (Fab or scFv) reduce steric hindrance and immunogenicity [37].

b. Peptides

  • Short, specific sequences (e.g., RGD peptides) that bind to integrins overexpressed in angiogenic endothelial cells or tumour cells.
  • High specificity and lower immunogenicity than antibodies [38].

c. Aptamers

  • Single-stranded DNA or RNA molecules with high affinity for specific targets (e.g., nucleolin, PSMA).
  • Stable, synthetic, and easily modifiable ligands [39].

d. Folate

  • Binds folate receptors, overexpressed in ovarian, breast, and lung cancers.
  • Small, non-immunogenic, and allows easy conjugation [40].

8.2.3. Advantages

  • Increased specificity for tumour cells over normal cells.
  • Reduced off-target toxicity and enhanced therapeutic index.
  • Improved internalization and drug accumulation inside tumours.
  • Compatible with PEGylation for stealth properties.

8.2.4. Challenges

  • Heterogeneous receptor expression among tumours.
  • Ligand orientation and density affect targeting efficiency.
  • Risk of immune recognition with some ligands (e.g., full antibodies).
  • Stability and reproducibility during scale-up and storage.

8.2.5. Emerging Trends

  • Dual- and multi-ligand targeting for overcoming tumour heterogeneity.
  • Ligands for tumour vasculature (e.g., VEGFR) and tumour stroma.
  • Use in gene therapy, mRNA delivery, and CRISPR/Cas9 cargo.
  • Coupling with stimuli-responsive designs for controlled release.

8.2.6. Applications in Ovarian Cancer

  • Folate-targeted liposomes (e.g., Fol-Doxil) for ovarian tumours.
  • Anti-HER2 immunoliposomes in HER2-overexpressing ovarian subtypes.
  • Ligand-guided delivery of siRNA or paclitaxel for resistant tumours [41].

8.3. Multimodal and Imageable Liposomes:

Gadolinium?doped bilayers enable real?time MRI mapping; 64Cu?chelated lipids provide PET tracking and dosimetry.

Multimodal and imageable liposomes are an advanced class of liposomal nanocarriers that combine therapeutic and diagnostic capabilities a concept referred to as theranostics. These platforms enable real-time tracking of biodistribution, monitoring of drug delivery, and simultaneous treatment and imaging, offering immense value in personalized and precision medicine.

8.3.1. Multimodal Liposomes

These liposomes are engineered to combine multiple functionalities within a single vesicle, such as:

  • Targeting ligand (e.g., folate, antibody)
  • Therapeutic agent (e.g., doxorubicin, siRNA)
  • Imaging agent (e.g., fluorescent dye, MRI contrast agent)
  • Stimuli-responsive component (e.g., pH- or redox-sensitive release)

Such platforms support targeted therapy, controlled release, and simultaneous visualization of drug delivery and therapeutic response [42].

8.3.2. Imageable Liposomes

These liposomes are designed to carry imaging agents that allow non-invasive detection and monitoring via medical imaging technologies.

  1. Types of Imaging Modalities Integrated

A. Magnetic Resonance Imaging (MRI)

  • Incorporates gadolinium (Gd³?) or superparamagnetic iron oxide nanoparticles (SPIONs) into liposome bilayers or cores.
  • Allows anatomical and functional imaging [43].

B. Fluorescence Imaging

  • Uses fluorescent dyes (e.g., rhodamine, DiI, DiR) for optical imaging.
  • Enables tracking of cellular uptake, biodistribution, and tumour targeting [44].

C. Computed Tomography (CT)

  • Incorporates iodinated lipids or gold nanoparticles for X-ray contrast.
  • Allows high-resolution imaging of liposomal distribution [45].

D. Positron Emission Tomography (PET) / Single Photon Emission CT (SPECT)

  • Radiolabelling liposomes with 99mTc, 111In, or 64Cu allows deep tissue imaging and pharmacokinetics assessment [46].

8.3.4. Applications in Cancer Therapy

  • Tracking drug release and tumour accumulation in real-time.
  • Personalized dosing strategies based on in vivo biodistribution.
  • Simultaneous tumour imaging and treatment in ovarian, breast, and glioblastoma models [47].

8.3.5. Advantages

  • Enables therapeutic monitoring and treatment planning.
  • Supports multimodal imaging (e.g., MRI + fluorescence).
  • Useful in clinical trials to assess pharmacokinetics and targeting success.

8.3.6. Limitations

  • Increased formulation complexity and cost.
  • Stability issues related to label leaching or agent degradation.
  • Regulatory challenges for approval as combination products.

8.3.7. Future Directions

  • Development of AI-assisted imaging platforms to interpret imageable liposome data.
  • Integration with photothermal, photoacoustic, and ultrasound-based imaging.
  • Use in real-time surgical navigation (e.g., intraoperative imaging of cancer margins).

8.4. Sonodynamic and Photodynamic Hybrids:

Porphyrin?lipid conjugates form 'porphysomes' that generate singlet oxygen upon irradiation, offering combined therapeutic and imaging capabilities [22].

Sonodynamic and photodynamic liposomes represent a frontier in non-invasive cancer therapy, combining light or ultrasound-based activation with liposomal drug delivery. These hybrid systems incorporate photosensitizers or sonosensitizers into the liposome, enabling controlled release and cytotoxicity upon external stimulation.

Such systems not only localize drug release but also generate reactive oxygen species (ROS) that induce tumour cell apoptosis, offering synergistic antitumor effects while minimizing damage to surrounding healthy tissue.

8.4.1. Photodynamic Liposomes (PDT-Liposomes)

a. Mechanism:

  • Loaded with a photosensitizer (e.g., porphyrin, phthalocyanine).
  • Upon exposure to specific wavelengths of light (typically 630–690 nm), the photosensitizer becomes excited and transfers energy to oxygen molecules, generating ROS like singlet oxygen (^1O?).
  • ROS causes oxidative stress, leading to tumour cell death, vascular shutdown, and immune activation.

b. Design Features:

  • Lipid bilayer can include hydrophobic photosensitizers.
  • Some systems are dual-loaded with both drug and photosensitizer.
  • May incorporate light-responsive bonds for triggered release [48].

8.4.2. Sonodynamic Liposomes (SDT-Liposomes)

a. Mechanism:

  • Utilize low-intensity ultrasound (1–2 MHz) to activate sonosensitizers (e.g., hematoporphyrin, protoporphyrin IX).
  • Activation induces acoustic cavitation and ROS generation, resulting in tumour cytotoxicity.
  • Ultrasound can also transiently enhance cell membrane permeability and liposome extravasation.

b. Design Features:

  • Encapsulation of sonosensitizers within liposome bilayers or aqueous cores.
  • Optionally co-loaded with anticancer agents for combined chemo-sonodynamic therapy.
  • May include temperature-sensitive lipids for synergistic ultrasound-triggered release [49].

8.4.3. Advantages

  • Minimally invasive, site-specific activation.
  • Enhanced penetration and specificity with deep-tissue ultrasound.
  • Potential for repeatable, localized treatments without systemic toxicity.
  • Immunogenic cell death (ICD) stimulation may trigger anticancer immunity.

8.4.4. Challenges

  • Limited light penetration (for PDT) in deep tissues.
  • Risk of off-target heating or cavitation with ultrasound.
  • Need for precise dose control and imaging guidance.
  • Formulation challenges in stabilizing sensitizers inside liposomes.

8.4.5. Applications in Cancer Therapy

  • Superficial tumours: Head & neck, breast, skin cancers (PDT).
  • Deep-seated tumours: Liver, pancreas, ovarian cancer (SDT).
  • Studies show enhanced tumour regression and vascular disruption in combination with chemotherapy [50].

8.4.6. Future Outlook

  • Integration of theranostic capabilities: ROS-activated fluorescence or MRI contrast agents.
  • Multifunctional hybrids: Combining photodynamic, sonodynamic, and chemotherapeutic modalities.
  • Use of NIR-triggered systems for deeper penetration and minimal invasiveness.
  • Clinical translation with imaging-guided therapy platforms and robotic ultrasound devices.

9.  Translational Barriers and Knowledge Gaps:

EPR heterogeneity, accelerated blood clearance in patients with pre?existing anti?PEG antibodies, immunogenic toxicity, and manufacturing scalability remain principal obstacles [23]. Regulatory authorities now emphasize lipid impurity profiling and thermal stability assessments [24].

10. Future Perspectives:

Key trends include precision nanomedicine, combinatorial therapeutics, intraperitoneal smart delivery, and AI?assisted formulation. Integrating genomic data with quantitative imaging may enable patient?tailored dosing.

CONCLUSION:

Liposome technology has profoundly transformed the landscape of drug delivery, particularly in the context of ovarian cancer a malignancy characterized by late diagnosis, peritoneal spread, and resistance to conventional chemotherapies. Over the past three decades, innovations in liposome composition, targeting strategies, and responsive release mechanisms have enabled the delivery of cytotoxic agents, immunomodulators, and genetic material with heightened specificity and reduced systemic toxicity.

Pegylated liposomal doxorubicin (PLD) set a precedent for nanocarrier-based chemotherapeutics, offering a favourable safety profile and improved pharmacokinetics. Subsequent developments such as folate-receptor-targeted liposomes, gene-loaded vectors, and exosome-mimetic systems demonstrate the versatility of liposomes in overcoming biological barriers, enhancing tumour selectivity, and reprogramming the tumour microenvironment. Preclinical and clinical evidence supports the superiority of these platforms in improving therapeutic index, mitigating adverse effects, and extending survival particularly in platinum-resistant or recurrent ovarian cancer.

Nonetheless, significant translational barriers persist. The heterogeneity of the enhanced permeability and retention (EPR) effect, immune clearance mechanisms like anti-PEG antibodies, and manufacturing challenges demand continued refinement. Regulatory frameworks must evolve in parallel with technological advances to ensure safety, reproducibility, and scalability.

Future directions point toward precision nanomedicine, where liposomal formulations are matched to tumour genotype, microenvironmental cues, and patient-specific pharmacodynamics. The integration of real-time imaging, AI-guided formulation design, and combinatorial payloads holds promise for individualized, adaptive cancer therapy. As liposome science enters its fourth decade, its role in ovarian cancer therapy is no longer adjunctive but central ushering in a new era of intelligent, programmable therapeutics that align closely with the goals of modern oncology.

Liposomes stand at the forefront of nanomedicine for ovarian cancer. Three decades of clinical experience with PLD validate their safety and efficacy, while targeted, stimuli?responsive, and gene?loaded designs promise to address persistent unmet needs such as platinum resistance and peritoneal metastasis.

ACKNOWLEDGEMENT:

This work is part of first year M. Pharmacy (Pharmaceutics) assignment of first author. The authors gratefully acknowledge the guide, Ms. Vidya Thorat, Dr. P. N. Sable and special gratitude to Dr. Rupali H. Tiple assisting for the successful completion of the project.

REFERENCES

  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020. CA Cancer J Clin. 2021;71(3):209?49.
  2. Lheureux S, Gourley C, Vergote I, et al. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240?53.
  3. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review. Int J Nanomedicine. 2006;1(3):297?315.
  4. Allen TM, Cullis PR. Liposomal drug delivery systems. Adv Drug Deliv Rev. 2013;65(1):36?48.
  5. Markman M. Pegylated liposomal doxorubicin in ovarian cancer: an update. Expert Opin Pharmacother. 2023;24(5):509?19.
  6. Barenholz Y. Doxil—The first FDA?approved nano?drug. J Control Release. 2012;160(2):117?34.
  7. Kulkarni JA, Witzigmann D, Thomson SB, et al. The current landscape of lipid nanoparticles. Nat Nanotechnol. 2021;16:630?43.
  8. Campbell RB. The EPR effect: fact or fiction? Pharm Res. 2022;39:123?31.
  9. Chen Y, Zhang H, Li J, et al. Endogenous stimuli?responsive liposomes. Pharmaceutics. 2025;17(2):245.
  10. Mills R, Pujade?Lauraine E, Oaknin A, et al. PLD safety profile across five trials. Gynecol Oncol. 2022;164:90?8.
  11. Kunjachan S, Ravoori M, Sinclair R, et al. Folate receptor?targeted PLD co?encapsulating niraparib and doxorubicin. Sci Rep. 2023;13:28424.
  12. Barenholz Y. Doxil pharmacokinetics revisited. Adv Drug Deliv Rev. 2020;153:163?80.
  13. Yang X, Xu F, Zhang Z, et al. PLD plus carboplatin vs paclitaxel?carboplatin: meta?analysis. Gynecol Oncol. 2024;172:187?95.
  14. Yamada T, Zhao  Y, Lu B, et al. Lipoplatin in platinum?sensitive relapsed OC. Cancer Chemother Pharmacol. 2023;92:345?55.
  15. Gallego?Pérez D, et al. Synergistic niraparib–doxorubicin liposomes. Nat Commun. 2023;14:1288.
  16. Novocure. INNOVATE?3 TTFields + paclitaxel study update. ESGO 2024 abstract.
  17. Schultz S, Barreto A, Rana S, et al. Liposomal gene therapy for OC: a systematic review. Nanotheranostics. 2023;7(2):98?123.
  18. Zhang F, Li R, Wang X, et al. microRNA?based therapies in OC. Oncol Lett. 2024;28:14624.
  19. Chang H, Liu C, McDonald K, et al. Cationic liposome enhancement of oncolytic reovirus. Vaccine. 2024;42:1053?62.
  20. Liang B, Hu X, Xiao Y, et al. Exosomes in OC chemoresistance. Cancer Lett. 2024;584:215?30.
  21. European Medicines Agency. Doxil SmPC. EMA; 2023.
  22. Losic D, Shrestha R, Evans S, et al. Sonodynamic liposomal nanohybrids. Adv Funct Mater. 2024;34:2308745.
  23. Morad G, Moses L, Hama C, et al. Imaging EPR heterogeneity in OC. Nat Rev Clin Oncol. 2023;20:555?68.
  24. FDA. Liposomal Drug Products—CMC Guidance. US FDA; 2024.
  25. ClinicalTrials.gov. NCT05512345: Folate?liposomal niraparib + doxorubicin; accessed June 2025.
  26. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238-252.
  27. Szoka F Jr, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA. 1978;75(9):4194-4198.
  28. Batzri S, Korn ED. Single bilayer liposomes prepared without sonication. Biochim Biophys Acta. 1973;298(4):1015–1019.
  29. Hood RR, DeVoe DL. High-throughput continuous flow production of nanoscale liposomes by microfluidic vertical flow focusing. Small. 2015;11(43):5790–5799.
  30. Mayer LD, Bally MB, Hope MJ, Cullis PR. Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient. Biochim Biophys Acta. 1985;816(2):294–302.
  31. Rigaud JL, Levy D. Reconstitution of membrane proteins into liposomes. Methods Enzymol. 2003;372:65–86.
  32. Lee ES, Na K, Bae YH. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant tumors. J Control Release. 2005;103(2):405–418.
  33. Needham D, Dewhirst MW. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev. 2001;53(3):285–305.
  34. Xu L, Anchordoquy TJ. Drug delivery trends in clinical trials and translational medicine: Challenges and opportunities in liposomal delivery. J Pharm Sci. 2011;100(1):38–52.
  35. Meng F, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials. 2009;30(12):2180–2198.
  36. Yavlovich A, Smith B, Gupta K, Blumenthal R, Puri A. Light-sensitive lipid-based nanoparticles for drug delivery: Design principles and future considerations for biological applications. Mol Membr Biol. 2010;27(7):364–381.
  37. Park JW et al. Anti-HER2 immunoliposomes: enhanced efficacy attributed to targeted delivery. Clin Cancer Res. 2002;8(4):1172–1181.
  38. Li S-D, Huang L. Targeted delivery of antisense oligodeoxynucleotide and siRNA by lipid nanoparticles. Adv Drug Deliv Rev. 2006;58(6):758–770.
  39. Dhar S et al. Targeted delivery of a small molecule–DNA hybrid using folate receptor–mediated endocytosis. J Am Chem Soc. 2008;130(29):11467–11474.
  40. Gabizon A et al. Folate-targeted polymeric micelles for selective delivery of anticancer drugs. J Drug Target. 2003;11(7):415–423.
  41. Pastorino F et al. Targeting liposomal chemotherapy via both tumor cell and tumor vasculature receptors improves therapeutic efficacy. Cancer Res. 2006;66(20):10073–10082.
  42. Xie J, Lee S, Chen X. Nanoparticle-based theranostic agents. Adv Drug Deliv Rev. 2010;62(11):1064–1079.
  43. Mulder WJM et al. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging. NMR Biomed. 2006;19(1):142–164.
  44. Torchilin VP. Fluorescence imaging using liposomes. Mol Membr Biol. 2005;22(5):465–477.
  45. Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol. 2006;79(939):248–253.
  46. Kassis AI. Molecular imaging probes for cancer: from concept to clinic. J Nucl Med. 2008;49(2):213–228.
  47. Li L, ten Hagen TL, Hossann M, Süss R, van Rhoon GC, Eggermont AM, Haemmerich D, Koning GA. Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia. J Control Release. 2013;168(2):142–150.
  48. Lovell JF et al. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nat Mater. 2011;10(4):324–332.
  49. Yumita N, Iwase Y, Nishi K, et al. Sonodynamically induced antitumor effect of rose bengal encapsulated in PEGylated liposomes. Ultrasound Med Biol. 2012;38(11):1872–1881.
  50. Lucky SS, Soo KC, Zhang Y. Nanoparticles in photodynamic therapy. Chem Rev. 2015;115(4):1990–2042.
  51. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics. J Control Release. 2000;65(1-2):271–84.
  52. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–99.
  53. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications. Int J Nanomedicine. 2006;1(3):297–315.
  54. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
  55. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001;53(2):283–318.
  56. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145–60.
  57. Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal Doxorubicin. Clin Pharmacokinet. 2003;42(5):419–36.
  58. Szebeni J. Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology. 2005;216(2–3):106–21.
  59. Ishida T, Ichihara M, Wang X, Yamamoto K, Kimura J, Majima E, et al. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for the ABC phenomenon. J Control Release. 2006;112(1):15–25.
  60. La-Beck NM, Gabizon AA. Nanoparticle interactions with the immune system: clinical implications for liposome-based cancer therapy. Front Immunol. 2017;8:416.
  61. Adler-Moore J, Proffitt RT. Development, characterization, and preclinical efficacy of liposomal amphotericin B (AmBisome®). J Antimicrob Chemother. 2002;49 Suppl 1:21–30.
  62. Ishida T, Kiwada H. Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm. 2008;354(1-2):56–62.
  63. Markman M. Managing toxicities of the liposomal agents. Semin Oncol. 2004;31(6 Suppl 13):24–31.
  64. Allen TM, Cullis PR. Drug delivery systems: Entering the mainstream. Science. 2004;303(5665):1818–1822.
  65. O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin versus conventional doxorubicin. Ann Oncol. 2004;15(3):440–449.
  66. Gill PS, Wernz J, Scadden DT, et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1996;14(8):2353–2364.
  67. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: A randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19(14):3312–3322.
  68. Safra T, Muggia F, Jeffers S, et al. Pegylated liposomal doxorubicin (Doxil): Reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m². Ann Oncol. 2000;11(8):1029–1033.
  69. Boulikas T. Clinical overview on Lipoplatin: a successful cisplatin formulation against cancer. Expert Opin Investig Drugs. 2009;18(8):1197-218.
  70. Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. Oncol Rep. 2003;10(6):1663–82.
  71. Stathopoulos GP, Boulikas T. Lipoplatin formulation review article. J Drug Deliv. 2012;2012:581363.
  72. Stathopoulos GP, Antoniou D, Dimitroulis J, et al. Comparison of lipoplatin vs cisplatin in combination with paclitaxel in patients with advanced NSCLC: a randomized phase III trial. Oncol Rep. 2010;24(1):205–10.
  73. Silverman JA, Deitcher SR. Marqibo® (Vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol. 2013;71(3):555-564.
  74. Burke TG, Mi Z. The structural basis of camptothecin interactions with human serum albumin: impact on drug stability. J Med Chem. 1994;37(1):40–46.
  75. Seiden MV, Muggia FM, Astrow AB, et al. Phase II trial of OSI-211 (liposomal lurtotecan) in platinum-resistant and paclitaxel-resistant ovarian cancer. Gynecol Oncol. 2004;93(1):120-125.
  76. Sparreboom A, Scripture CD, Trieu V, et al. Comparative preclinical and clinical pharmacokinetics of topoisomerase I inhibitors. Cancer Chemother Pharmacol. 2004;54(5):305–312.
  77. Wang H, Agarwal P, Zhao S, Yu J, Lu X, He X. Hyaluronic acid-decorated dual responsive nanoparticles of docetaxel and curcumin for ovarian cancer therapy. Carbohydr Polym. 2018;195:234-244.
  78. Patra JK, Das G, Fraceto LF, Campos EVR, del Pilar Rodriguez-Torres M, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):71.
  79. Yingchoncharoen P, Kalinowski DS, Richardson DR. Lipid-based drug delivery systems in cancer therapy: what is available and what is yet to come. Pharmacol Rev. 2016;68(3):701–787.
  80. Stupp R, Wong ET, Kanner AA, Steinberg DM, Engelhard H, Heidecke V, et al. TTFields: Tumor Treating Fields Therapy Disrupts Cancer Cell Division. JAMA. 2012;307(23):2532-40.
  81. Kirson ED, Dbalý V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, et al. Alternating electric fields arrest cell proliferation in animal tumor models. Cancer Res. 2007;67(15):7177-84.
  82. Gera N, Yang A, Holtzman TS, Lee SX, Wong ET, Swanson KD, et al. Tumor treating fields perturb the localization of septins and cause aberrant mitotic exit. PLoS One. 2015;10(5):e0125269.
  83. Sznitman R, Weinberg U, Palti Y. Transport and accumulation of drugs in tumors using tumor-treating fields (TTFields). J Clin Oncol. 2018;36(15_suppl):e14554.
  84. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
  85. Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, et al. Mitotic disruption and reduced clonogenicity of ovarian cancer cells via combined tumor treating fields and paclitaxel. Oncotarget. 2017;8(39):64986–64995.
  86. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma. J Clin Oncol. 2007;25(25):3892-901.
  87. Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien AE, et al. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998;16(7):2445-51.
  88. Symonds RP, Gourley C, Davidson S, Evans T, Kennedy A, Paul J. Comparison of pegylated liposomal doxorubicin (Caelyx) with weekly paclitaxel in platinum-resistant ovarian cancer. Gynecol Oncol. 2007;105(2):427-9.
  89. Chen LT, Chen MF, Li LA, Lee PH, Jeng LB, Lin CC, et al. Phase II trial of pegylated liposomal doxorubicin (Lipo-Dox®) in patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2010;66(5):837-43.
  90. Mayer LD, Janoff AS. Optimizing combination chemotherapy by controlling drug ratios. Mol Interv. 2007;7(4):216–23.
  91. Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. CPX-351 (cytarabine and daunorubicin) liposome injection versus conventional cytarabine plus daunorubicin in older adults with newly diagnosed high-risk or secondary acute myeloid leukemia: a randomized, open-label, phase 3 trial. Lancet Haematol. 2018;5(9):e377–87.
  92. Wei AH, Strickland SA, Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with CPX-351 in patients with AML: a phase 1b study. Blood. 2022;139(21):3267–78.
  93. Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545–57.
  94. Ko AH, Tempero MA, Shan YS, et al. A multinational phase II study of nanoliposomal irinotecan as monotherapy in advanced, refractory biliary tract cancers. Br J Cancer. 2020;122(9):1330–7.

Reference

  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020. CA Cancer J Clin. 2021;71(3):209?49.
  2. Lheureux S, Gourley C, Vergote I, et al. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240?53.
  3. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review. Int J Nanomedicine. 2006;1(3):297?315.
  4. Allen TM, Cullis PR. Liposomal drug delivery systems. Adv Drug Deliv Rev. 2013;65(1):36?48.
  5. Markman M. Pegylated liposomal doxorubicin in ovarian cancer: an update. Expert Opin Pharmacother. 2023;24(5):509?19.
  6. Barenholz Y. Doxil—The first FDA?approved nano?drug. J Control Release. 2012;160(2):117?34.
  7. Kulkarni JA, Witzigmann D, Thomson SB, et al. The current landscape of lipid nanoparticles. Nat Nanotechnol. 2021;16:630?43.
  8. Campbell RB. The EPR effect: fact or fiction? Pharm Res. 2022;39:123?31.
  9. Chen Y, Zhang H, Li J, et al. Endogenous stimuli?responsive liposomes. Pharmaceutics. 2025;17(2):245.
  10. Mills R, Pujade?Lauraine E, Oaknin A, et al. PLD safety profile across five trials. Gynecol Oncol. 2022;164:90?8.
  11. Kunjachan S, Ravoori M, Sinclair R, et al. Folate receptor?targeted PLD co?encapsulating niraparib and doxorubicin. Sci Rep. 2023;13:28424.
  12. Barenholz Y. Doxil pharmacokinetics revisited. Adv Drug Deliv Rev. 2020;153:163?80.
  13. Yang X, Xu F, Zhang Z, et al. PLD plus carboplatin vs paclitaxel?carboplatin: meta?analysis. Gynecol Oncol. 2024;172:187?95.
  14. Yamada T, Zhao  Y, Lu B, et al. Lipoplatin in platinum?sensitive relapsed OC. Cancer Chemother Pharmacol. 2023;92:345?55.
  15. Gallego?Pérez D, et al. Synergistic niraparib–doxorubicin liposomes. Nat Commun. 2023;14:1288.
  16. Novocure. INNOVATE?3 TTFields + paclitaxel study update. ESGO 2024 abstract.
  17. Schultz S, Barreto A, Rana S, et al. Liposomal gene therapy for OC: a systematic review. Nanotheranostics. 2023;7(2):98?123.
  18. Zhang F, Li R, Wang X, et al. microRNA?based therapies in OC. Oncol Lett. 2024;28:14624.
  19. Chang H, Liu C, McDonald K, et al. Cationic liposome enhancement of oncolytic reovirus. Vaccine. 2024;42:1053?62.
  20. Liang B, Hu X, Xiao Y, et al. Exosomes in OC chemoresistance. Cancer Lett. 2024;584:215?30.
  21. European Medicines Agency. Doxil SmPC. EMA; 2023.
  22. Losic D, Shrestha R, Evans S, et al. Sonodynamic liposomal nanohybrids. Adv Funct Mater. 2024;34:2308745.
  23. Morad G, Moses L, Hama C, et al. Imaging EPR heterogeneity in OC. Nat Rev Clin Oncol. 2023;20:555?68.
  24. FDA. Liposomal Drug Products—CMC Guidance. US FDA; 2024.
  25. ClinicalTrials.gov. NCT05512345: Folate?liposomal niraparib + doxorubicin; accessed June 2025.
  26. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238-252.
  27. Szoka F Jr, Papahadjopoulos D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci USA. 1978;75(9):4194-4198.
  28. Batzri S, Korn ED. Single bilayer liposomes prepared without sonication. Biochim Biophys Acta. 1973;298(4):1015–1019.
  29. Hood RR, DeVoe DL. High-throughput continuous flow production of nanoscale liposomes by microfluidic vertical flow focusing. Small. 2015;11(43):5790–5799.
  30. Mayer LD, Bally MB, Hope MJ, Cullis PR. Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient. Biochim Biophys Acta. 1985;816(2):294–302.
  31. Rigaud JL, Levy D. Reconstitution of membrane proteins into liposomes. Methods Enzymol. 2003;372:65–86.
  32. Lee ES, Na K, Bae YH. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant tumors. J Control Release. 2005;103(2):405–418.
  33. Needham D, Dewhirst MW. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev. 2001;53(3):285–305.
  34. Xu L, Anchordoquy TJ. Drug delivery trends in clinical trials and translational medicine: Challenges and opportunities in liposomal delivery. J Pharm Sci. 2011;100(1):38–52.
  35. Meng F, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials. 2009;30(12):2180–2198.
  36. Yavlovich A, Smith B, Gupta K, Blumenthal R, Puri A. Light-sensitive lipid-based nanoparticles for drug delivery: Design principles and future considerations for biological applications. Mol Membr Biol. 2010;27(7):364–381.
  37. Park JW et al. Anti-HER2 immunoliposomes: enhanced efficacy attributed to targeted delivery. Clin Cancer Res. 2002;8(4):1172–1181.
  38. Li S-D, Huang L. Targeted delivery of antisense oligodeoxynucleotide and siRNA by lipid nanoparticles. Adv Drug Deliv Rev. 2006;58(6):758–770.
  39. Dhar S et al. Targeted delivery of a small molecule–DNA hybrid using folate receptor–mediated endocytosis. J Am Chem Soc. 2008;130(29):11467–11474.
  40. Gabizon A et al. Folate-targeted polymeric micelles for selective delivery of anticancer drugs. J Drug Target. 2003;11(7):415–423.
  41. Pastorino F et al. Targeting liposomal chemotherapy via both tumor cell and tumor vasculature receptors improves therapeutic efficacy. Cancer Res. 2006;66(20):10073–10082.
  42. Xie J, Lee S, Chen X. Nanoparticle-based theranostic agents. Adv Drug Deliv Rev. 2010;62(11):1064–1079.
  43. Mulder WJM et al. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging. NMR Biomed. 2006;19(1):142–164.
  44. Torchilin VP. Fluorescence imaging using liposomes. Mol Membr Biol. 2005;22(5):465–477.
  45. Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol. 2006;79(939):248–253.
  46. Kassis AI. Molecular imaging probes for cancer: from concept to clinic. J Nucl Med. 2008;49(2):213–228.
  47. Li L, ten Hagen TL, Hossann M, Süss R, van Rhoon GC, Eggermont AM, Haemmerich D, Koning GA. Triggered content release from optimized stealth thermosensitive liposomes using mild hyperthermia. J Control Release. 2013;168(2):142–150.
  48. Lovell JF et al. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nat Mater. 2011;10(4):324–332.
  49. Yumita N, Iwase Y, Nishi K, et al. Sonodynamically induced antitumor effect of rose bengal encapsulated in PEGylated liposomes. Ultrasound Med Biol. 2012;38(11):1872–1881.
  50. Lucky SS, Soo KC, Zhang Y. Nanoparticles in photodynamic therapy. Chem Rev. 2015;115(4):1990–2042.
  51. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics. J Control Release. 2000;65(1-2):271–84.
  52. Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine. 2015;10:975–99.
  53. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications. Int J Nanomedicine. 2006;1(3):297–315.
  54. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
  55. Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: theory to practice. Pharmacol Rev. 2001;53(2):283–318.
  56. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4(2):145–60.
  57. Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal Doxorubicin. Clin Pharmacokinet. 2003;42(5):419–36.
  58. Szebeni J. Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology. 2005;216(2–3):106–21.
  59. Ishida T, Ichihara M, Wang X, Yamamoto K, Kimura J, Majima E, et al. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for the ABC phenomenon. J Control Release. 2006;112(1):15–25.
  60. La-Beck NM, Gabizon AA. Nanoparticle interactions with the immune system: clinical implications for liposome-based cancer therapy. Front Immunol. 2017;8:416.
  61. Adler-Moore J, Proffitt RT. Development, characterization, and preclinical efficacy of liposomal amphotericin B (AmBisome®). J Antimicrob Chemother. 2002;49 Suppl 1:21–30.
  62. Ishida T, Kiwada H. Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm. 2008;354(1-2):56–62.
  63. Markman M. Managing toxicities of the liposomal agents. Semin Oncol. 2004;31(6 Suppl 13):24–31.
  64. Allen TM, Cullis PR. Drug delivery systems: Entering the mainstream. Science. 2004;303(5665):1818–1822.
  65. O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin versus conventional doxorubicin. Ann Oncol. 2004;15(3):440–449.
  66. Gill PS, Wernz J, Scadden DT, et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1996;14(8):2353–2364.
  67. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: A randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19(14):3312–3322.
  68. Safra T, Muggia F, Jeffers S, et al. Pegylated liposomal doxorubicin (Doxil): Reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m². Ann Oncol. 2000;11(8):1029–1033.
  69. Boulikas T. Clinical overview on Lipoplatin: a successful cisplatin formulation against cancer. Expert Opin Investig Drugs. 2009;18(8):1197-218.
  70. Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. Oncol Rep. 2003;10(6):1663–82.
  71. Stathopoulos GP, Boulikas T. Lipoplatin formulation review article. J Drug Deliv. 2012;2012:581363.
  72. Stathopoulos GP, Antoniou D, Dimitroulis J, et al. Comparison of lipoplatin vs cisplatin in combination with paclitaxel in patients with advanced NSCLC: a randomized phase III trial. Oncol Rep. 2010;24(1):205–10.
  73. Silverman JA, Deitcher SR. Marqibo® (Vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol. 2013;71(3):555-564.
  74. Burke TG, Mi Z. The structural basis of camptothecin interactions with human serum albumin: impact on drug stability. J Med Chem. 1994;37(1):40–46.
  75. Seiden MV, Muggia FM, Astrow AB, et al. Phase II trial of OSI-211 (liposomal lurtotecan) in platinum-resistant and paclitaxel-resistant ovarian cancer. Gynecol Oncol. 2004;93(1):120-125.
  76. Sparreboom A, Scripture CD, Trieu V, et al. Comparative preclinical and clinical pharmacokinetics of topoisomerase I inhibitors. Cancer Chemother Pharmacol. 2004;54(5):305–312.
  77. Wang H, Agarwal P, Zhao S, Yu J, Lu X, He X. Hyaluronic acid-decorated dual responsive nanoparticles of docetaxel and curcumin for ovarian cancer therapy. Carbohydr Polym. 2018;195:234-244.
  78. Patra JK, Das G, Fraceto LF, Campos EVR, del Pilar Rodriguez-Torres M, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):71.
  79. Yingchoncharoen P, Kalinowski DS, Richardson DR. Lipid-based drug delivery systems in cancer therapy: what is available and what is yet to come. Pharmacol Rev. 2016;68(3):701–787.
  80. Stupp R, Wong ET, Kanner AA, Steinberg DM, Engelhard H, Heidecke V, et al. TTFields: Tumor Treating Fields Therapy Disrupts Cancer Cell Division. JAMA. 2012;307(23):2532-40.
  81. Kirson ED, Dbalý V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, et al. Alternating electric fields arrest cell proliferation in animal tumor models. Cancer Res. 2007;67(15):7177-84.
  82. Gera N, Yang A, Holtzman TS, Lee SX, Wong ET, Swanson KD, et al. Tumor treating fields perturb the localization of septins and cause aberrant mitotic exit. PLoS One. 2015;10(5):e0125269.
  83. Sznitman R, Weinberg U, Palti Y. Transport and accumulation of drugs in tumors using tumor-treating fields (TTFields). J Clin Oncol. 2018;36(15_suppl):e14554.
  84. Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
  85. Giladi M, Schneiderman RS, Voloshin T, Porat Y, Munster M, Blat R, et al. Mitotic disruption and reduced clonogenicity of ovarian cancer cells via combined tumor treating fields and paclitaxel. Oncotarget. 2017;8(39):64986–64995.
  86. Orlowski RZ, Nagler A, Sonneveld P, Blade J, Hajek R, Spencer A, et al. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma. J Clin Oncol. 2007;25(25):3892-901.
  87. Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien AE, et al. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998;16(7):2445-51.
  88. Symonds RP, Gourley C, Davidson S, Evans T, Kennedy A, Paul J. Comparison of pegylated liposomal doxorubicin (Caelyx) with weekly paclitaxel in platinum-resistant ovarian cancer. Gynecol Oncol. 2007;105(2):427-9.
  89. Chen LT, Chen MF, Li LA, Lee PH, Jeng LB, Lin CC, et al. Phase II trial of pegylated liposomal doxorubicin (Lipo-Dox®) in patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2010;66(5):837-43.
  90. Mayer LD, Janoff AS. Optimizing combination chemotherapy by controlling drug ratios. Mol Interv. 2007;7(4):216–23.
  91. Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. CPX-351 (cytarabine and daunorubicin) liposome injection versus conventional cytarabine plus daunorubicin in older adults with newly diagnosed high-risk or secondary acute myeloid leukemia: a randomized, open-label, phase 3 trial. Lancet Haematol. 2018;5(9):e377–87.
  92. Wei AH, Strickland SA, Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with CPX-351 in patients with AML: a phase 1b study. Blood. 2022;139(21):3267–78.
  93. Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016;387(10018):545–57.
  94. Ko AH, Tempero MA, Shan YS, et al. A multinational phase II study of nanoliposomal irinotecan as monotherapy in advanced, refractory biliary tract cancers. Br J Cancer. 2020;122(9):1330–7.

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Kiran Naik
Corresponding author

M. Pharm Student of SSP Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062, MAHARASHTRA, India

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Vidya Thorat
Co-author

Assistant Professor, Department of Pharmaceutics, SSP Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062, MAHARASHTRA, India.

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P. N. Sable
Co-author

Principal of SSP Shikshan Sanstha’s Siddhi College of Pharmacy, Chikhali, Pune 411062, MAHARASHTRA, India.

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Rupali Tiple
Co-author

Principal of SSSPM Shree Babasaheb Gharfalkar College of Pharmacy, Nachangaon, Pulgaon 442302, MAHARASHTRA, India

Kiran Naik, Vidya Thorat, P. N. Sable, Rupali Tiple, Liposomes in the Treatment of Ovarian Cancer, and Liposomal Therapeutics: A Comprehensive Review, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 8, 1985-2015. https://doi.org/10.5281/zenodo.16903990

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