Department of pharmaceutics, R.C. Patel Institute of Pharmacy, karvand naka, Shirpur. District Dhule pin code 425405(MS).
Phytosomes, a novel vesicular drug delivery system, have emerged as a promising approach to enhancing the bioavailability and therapeutic efficacy of poorly soluble phytochemicals. By forming stable lipid complexes, phytosomes improve solubility, absorption, and pharmacokinetic profiles, thereby overcoming the limitations of conventional herbal formulations. Recent advances have focused on optimizing phytosomes technology for various applications, including Hepato protection, neuroprotection, and cancer therapy. Patented technologies have introduced novel phytosomes-based formulations for targeted drug delivery and enhanced therapeutic outcomes. Despite their potential, regulatory challenges, scalability, and cost-related concerns hinder widespread commercialization. For phytosomes-based medicines to be incorporated into contemporary medicine, standardization of regulatory mechanisms and production procedures is essential. With an emphasis on recent patents and their uses in medicine, this study examines the pharmacological, structural, and mechanistic aspects of phytosomes. Phytosomes can help close the gap between contemporary pharmaceutical research and traditional herbal therapy by tackling formulation issues and regulatory barriers.
For centuries, medicinal herbs and their bioactive components have been integral to the treatment of various diseases. Nonetheless, despite their therapeutic promise, several challenges impede their clinical application. A significant factor contributing to the renewed interest in herbal medicines is the inadequacy of modern pharmaceuticals in effectively addressing all health conditions, coupled with concerns regarding the safety and side effects associated with synthetic drugs. Numerous studies suggest that compounds derived from plants frequently demonstrate superior efficacy with fewer adverse effects. However, their limited oral bioavailability presents a substantial barrier to clinical use like quercetin(1), ,thymoquinone (TQ)(2), piperine,(3) To mitigate these challenges, various formulation strategies have been proposed, including emulsions, liposomes, nano-formulations, molecular modifications, and prodrug administration. Among these strategies, phyto-phospholipid complexes, commonly referred to as phytosomes, have emerged as a promising method to enhance the absorption and bioavailability of herbal bioactives. The term "phytosome" is derived from "phyto" (meaning plant) and "some" (indicating a cell-like structure). Phytosomes, also known as herbosomes, represent advanced vesicular drug delivery systems designed to improve the pharmacokinetic and pharmacological properties of poorly soluble phytoconstituents. They are created by complexing phospholipids with plant extracts or phytochemicals in an aprotic solvent, resulting in a stable and bioavailable formulation. In contrast to conventional herbal extracts, phytosomes demonstrate higher drug encapsulation efficiency, enhanced stability, and superior absorption due to the strong interactions between the polar heads of phospholipids and phytoconstituents. This interaction enhances solubility, leading to improved gastrointestinal uptake and augmented therapeutic effects.
Figure no 1: Difference between phytosomes and liposome
Structurally, phytosomes differ from liposomes. While liposomes encapsulate hydrophilic compounds within their aqueous core, phytosomes incorporate bioactive phytochemicals as integral components of their phospholipid structure through hydrogen bonding and polar interactions. This configuration enables phytosomes to effectively deliver both hydrophilic and lipophilic compounds, thereby overcoming solubility challenges. In the field of oncology, phytosomes have garnered attention for their potential role in cancer therapy(4). Their capacity to evade the immune system facilitates passive targeting, while their nanoscale size and molecular weight (greater than 40 kDa) promote active targeting through the enhanced permeability and retention (EPR) effect in tumor tissues. These mechanisms enhance drug bioavailability and site- specific delivery, thereby minimizing the systemic toxicity commonly associated with chemotherapy.
Originally developed for cosmetic applications, phytosomes have since been extensively investigated in the pharmaceutical domain. Research underscores their efficacy in anti-inflammatory(5), hepatoprotective(6), cardiovascular(7), and anticancer treatments(8). Their straightforward manufacturing process and robust chemical interactions ensure minimal degradation of bioactive compounds, establishing phytosomes as a reliable herbal drug delivery system. Given their improved bioavailability and therapeutic potential, phytosomes present a promising alternative to conventional cancer therapies. This review aims to provide a comprehensive analysis of their formulation, characterization, mechanisms of action, applications, and future prospects in cancer diagnosis and treatment.
Phytochemicals and Their Therapeutic Significance
Phytochemicals are naturally occurring bioactive compounds found in plants, known for their diverse pharmacological and nutritional benefits. These compounds contribute to a plant’s color, aroma, and flavor while also playing a protective role. Based on their structural characteristics, phytochemicals are broadly classified into three major categories: terpenoids(9), alkaloids(10), and polyphenolic compounds(11). Many phytochemicals exhibit poor water solubility, low permeability, and rapid metabolic degradation, leading to poor bioavailability. Factors such as high molecular weight, multiple ring structures, and poor lipid solubility restrict their absorption in the gastrointestinal tract. Additionally, enzymatic degradation and first-pass metabolism further reduce their systemic availability, limiting their therapeutic efficacy. These challenges necessitate the development of advanced drug delivery systems to enhance the pharmacokinetic profile of phytochemicals.
Structure of Phytosomes and mechanism of formulation
Phytosomes are plant extract-phospholipid complexes formed by binding individual components of an herbal extract to phosphatidylcholine, a lipid component of cell membranes.
Figure No. 2: Structure of Phytosomes
Phytosomes are vesicular drug delivery systems made out of plant extracts rich in active phytoconstituents such as flavonoids(12), terpenoids(13), and glycosides(14). They are made from phospholipids, usually phosphatidylcholine from soy or sunflower lecithin. They are structurally composed of a hydrophilic outer layer of phospholipid heads and a lipophilic inner core containing the plant extract. Phytosomes are typically spherical or vesicular in shape, with sizes ranging from 50 to 100 nm, which improves the bioavailability of herbal chemicals.
Mechanism of formulation
Figure no 3: Mechanism of formulation
Common preparation techniques of Phytosomes
Solvent evaporation method
The solvent evaporation approach for phytosomes production entails dissolving phospholipids and bioactive chemicals in an organic solvent such as chloroform or ethanol. The mixture is then subjected to rotary evaporation at low pressure to remove the solvent, resulting in the development of a thin lipid layer. This film is hydrated with an aqueous phase, then sonicated or homogenized to produce homogenous phytosomes. Utilizing the solvent evaporation method to increase bioavailability, silymarin-containing phytosomes demonstrated stability, a 133.53 nm vesicle size, and an entrapment efficiency of 97.17%. Spectroscopy and microscopy verified the successful formation of the complex and the integrity of the vesicles.(15)
Figure no 4: Solvent evaporation method
Anti-precipitation method
In order to prepare phytosomes using the antisolvent evaporation approach, bioactive substances and phospholipids must be dissolved in an appropriate organic solvent, such as methanol, ethanol, or chloroform. In order to create a stable phytosomal complex, an antisolvent—usually water or a hydroalcoholic solution—is then progressively added to cause precipitation. After that, the organic solvent is removed, guaranteeing the phytosomes' better stability and appropriate encapsulation. The bioavailability and therapeutic effectiveness of poorly soluble bioactive chemicals are improved by this technique. Utilizing the antisolvent precipitation method, Murraya koenigii phytosomes created to improve their antidiabetic qualities. When administered to diabetic Wistar rats, the optimized formulation (236 nm, 75.1% entrapment) dramatically decreased serum glucose levels, indicating better therapeutic efficacy than the crude extract.(16)
Figure no 5: Anti-precipitation method
Thin hydration method the typical thin-film hydration technique for making phytosomes entails dissolving bioactive substances and phospholipids in an organic solvent, such as methanol or chloroform. A thin film is created following solvent evaporation, and when it is hydrated with an aqueous phase, stable, nanoscale vesicles with improved bioavailability are produced. The thin-film hydration method was used to synthesize the enhanced pomegranate peel extract into nano-phytosomes, which had a one-year stability and a 58% encapsulation efficiency with a particle size of 154.0–216.5 nm. Resin column chromatography, which was previously optimized at a 3:1 resin-to-extract ratio, improved bioavailability and functioning by increasing phenolic content 2.63 times with an 80.50% yield(17).
Lyophilization Method: Phospholipids and bioactive substances are dissolved in an organic solvent to form a lipid complex in the popular lyophilization procedure for phytosome production. After that, the combination is frozen and freeze-dried, producing a stable, dry powder with improved bioavailability and solubility freeze-drying technique were used to create NPDPIs, innovative Naringenin-Loaded Dipalmitoyl phosphatidylcholine Phytosome for inhalation. In a rat model of acute lung injury, they showed excellent stability, pulmonary bioavailability, and anti-inflammatory properties, making them a potentially effective clinical treatment.(18)
Figure no 6: Lyophilization Method
Characterization of phytosomes
Drug entrapment and loading capacity. The drug phytosomal complex was centrifuged at 10000 rpm for 90 minutes at 4°C to separate the phytosomes from the remaining drug. Ultraviolet spectroscopy can measure the concentration of free drugs. EE %= ???????? ÷ ???????? × 100 ,where IP is the initial phytochemical content and EP is the encapsulated phytochemical. Dialysis, ultracentrifugation, or Sephadex gel are used to eliminate free, unencapsulated phytochemicals. (19)
Particle size and zeta potential are important properties of complexes that are related to stability and reproducibility. In general, the average phospholipid complexes particle size ranged from 50 nm to 100 µm Zeta potential is measured using a variety of methods, such as Doppler velocimetry, micro electrophoresis, and DLS( Dynamic Light Scattering )devices. Using the Doppler Effect in a laser beam, laser Doppler velocimetry evaluates the mobility of phytosomes. (20)
Structural and interaction studies:
X-ray diffraction is a useful technique for analyzing the microstructure of some amorphous and crystal materials. Active constituents or active constituent phyto-phospholipid complexes, PCs, and their physical combinations are typically the subjects of X-ray diffraction. A high crystal form is indicated by intense crystalline peaks in the X-ray diffraction of a physical mixture and an active ingredient. The absence of a crystalline peak in phyto-phospholipid complexes with active ingredients, on the other hand, indicates that the constituents in the complex with phospholipids have an amorphous or molecular form.(21)
Patented technologies in Phytosomes
Table no: 1 patented technologies in Phytosomes
|
Patent no |
Phytochemical |
Findings |
Year |
|||
|
EP1844785
|
Olive fruit/leaf extracts |
Enhanced bioavailability when formulated as phospholipid complexes. |
(22) |
|||
|
WO2009/101551
|
|
Phospholipid complexes of curcumin provide higher systemic levels than uncomplexed curcumin. |
(23) |
|||
|
US2007/0015698
|
Thymosin β-4 |
Formulation containing Thymosin β-4 for wound healing and skin treatment |
(24) |
|||
|
Centella asiatica triterpenes, Vitis vinifera extracts, Ginkgo biloba flavonoids |
Oral compositions for cellulite treatment using these phytochemicals in free or complexed form with phospholipids. |
(25) |
|||
|
EP1813280
|
Ginkgo biloba derivatives |
Compositions for the treatment of asthmatic and allergic conditions |
(26) |
|||
|
WO/2004/045541
|
|
Soluble isoflavone compositions with improved solubility and texture characteristics |
(19) |
|||
|
Curcumin, piperine |
Phospholipid-curcumin complex and piperine formulation for enhanced bioavailability. |
(27) |
|||
|
|
Saponin-phospholipid phytosome complexes with improved properties. |
(28) |
|||
|
Centella asiatica extracts |
Phytosome comprising Centella asiatica extracts and the method of preparing thereof. |
(29) |
|||
|
|
Phytosome-based transdermal drug delivery system comprising curcumin for psoriasis treatment. |
(13) |
|||
|
|
Phytosome formulations for enhanced bioavailability of silybin. |
(30) |
|||
|
|
Use of phytosomal curcumin in liver cancer treatment. |
(8) |
|||
|
Polyherbal formulation |
Phytosome-based hepato-targeted synergistic polyherbal formulation for liver disorder treatment. |
(31) |
Marketed Phytosomal products
Table no :2 Marketed Phytosomal products
|
Product |
Phytochemical |
Findings |
Year |
||
|
Siliphos®
|
Silybin from Silybum marianum |
Hepatoprotective and antioxidant properties |
(32) |
||
|
Ginsenosides from Panax ginseng |
Immunomodulatory effects. |
(33) |
||
|
Flavonoids from Ginkgo biloba |
Anti-aging effects and support for brain vascular health. |
(34) |
||
|
Polyphenols from Olea europaea |
Anti-inflammatory and antihyperlipidemic effects. |
(35) |
||
|
Echinacosides from Echinacea angustifolia |
Immunomodulatory properties and use as a nutraceutical |
(36) |
||
|
Polyphenols from Camellia sinensis |
Supports body weight balance and exhibits antioxidant activity |
(37) |
||
|
Polyphenols from Vitis vinifera |
Cardiovascular support and antioxidant activities |
(38) |
||
|
Curcuminoids from Curcuma longa |
Anti-inflammatory effects; supports joint health and healthy inflammatory response |
(39) |
||
|
|
antioxidant and anti-inflammatory effects |
(40) |
Conclusion and Future Perspectives
Drug delivery has advanced significantly with phytosomes, which solve the long-standing problem of many phytochemicals' low bioavailability. Phytosomes improve plant-derived bioactives' solubility, absorption, and therapeutic effectiveness by combining with phospholipids to create stable complexes. Their use in a variety of therapeutic domains, such as neurology, cardiology, cancer, and metabolic disorders, demonstrates their adaptability in contemporary medicine. To fully realize their potential, however, future studies should concentrate on enhancing targeted delivery by ligand changes, using nanotechnology for improved stability and controlled release, and streamlining large-scale production processes to reduce expenses. In order to guarantee the safety, effectiveness, and market acceptance of phytosomal formulations globally, regulatory standardization is also crucial. Personalized medicine has the potential to improve treatment results by customizing phytosomes according to genetic and metabolic profiles. Phytosomes are revolutionizing the role of herbal medicine in pharmaceutical development by providing a natural but cutting-edge scientific substitute for manufactured medications. They are very effective in cancer treatment because of their capacity to improve pharmacokinetics, which increases drug retention in tumor tissues, improves cardiovascular health by improving flavonoid absorption, and helps neuroprotective agents like curcumin and ginkgo biloba better penetrate the blood- brain barrier. Phytosomes also aid in the treatment of metabolic diseases including diabetes and obesity. They are also used in dermatology to improve the skin's absorption of anti-aging and antioxidant substances. The gap between conventional herbal therapy and contemporary drug delivery technologies will be closed as research into phytosomal technology advances and becomes more widely used in pharmaceuticals.
REFERENCES
Janhavi Gorane*, Kamlesh Mali, Phytosomes: A Novel Vesicular System for Enhanced Bioavailability and Therapeutic Efficacy, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 4936-4946. https://doi.org/10.5281/zenodo.15553772
10.5281/zenodo.15553772
