Revolutionizing Drug Delivery: Spanlastics as Adaptive Nanovesicular Platforms for Multimodal Therapeutics

Keshav Maurya , Sobhna Singh, Neha,

doi:10.5281/zenodo.19909752

Review Paper | Open Access
Volume 04 | Issue 04 | Article Id IJPS/260404586

Revolutionizing Drug Delivery: Spanlastics as Adaptive Nanovesicular Platforms for Multimodal Therapeutics
Keshav Maurya * Sobhna Singh Neha
Department of Pharmacy, Mahatma Jyotiba Phule Rohilkhand University Bareilly 243001, Uttar Pradesh, India.

Abstract

In 2011, Spanlastics were first made available. An elastic system composed of the edge activator and non-ionic surfactant is the spanlastics, a novel elastic nanovesicle carrier. Drugs that are lipophilic or lipophobic can be delivered via SPs. This nanocarrier system are encapsulated in compartment composed of outer lipid and interior hydrophilic layers. These are vesicular carriers that are nontoxic, biodegradable, and nonimmunogenic. Multiple studies have shown that SPs can reduce side effects, increase therapeutic efficacy, improve medication absorption, and increase patient compliance. These vesicular vehicles also perform better in terms of chemical stability than liposomes due to their flexibility, and they have other benefits over the niosomal colloidal delivery systems. Additionally, by functioning as a disruptive agent and enhancing deformability against biological membranes, edge activator residency in the vesicle lipid membrane increases the permeability of nano-sized vesicles, both of which are acknowledged advantages of spanlastic vesicles elasticity.An aqueous solute solution is fully encapsulated inside them. They have been shown to be more chemically stable. In addition to providing targeted and regulated release of natural therapeutic components, they have corrected a number of shortcomings of the conventional dosage form. By delivering the active medicinal ingredients in a targeted manner and controlling their release rate, they address a number of problems related to the traditional dosage form. Emphasizing the value of SPs, their permeation mechanism, evaluation criteria, various preparation methodology, and applications is the aim of this review

Keywords

Nanotechnology, Spanlastics, Surfactant, Transdermal permeability, Vesicular drug delivery syetem

Introduction

Paul Ehrlich discovered a medication delivery method that would directly target sick cells in the 1990s, he started the research of targeted drug delivery system. Like transferosomes, these are extremely elastic and malleable carrier. Compared to the drug solution and these deformable vesicular carrier systems exhibit better penetration.1

A novel kind of elastic vesicular nanocarrier known as spanlastics traps the medication in the core cavity as a bilayer. Surfactant, which are made up of spans and edge activator are the basis for the word “Spanlastic” (Span+Elastic). Spanlastics, a novel drug delivery technology, were introduced in 2011.2 An elastic system composed of the edge- activator and non-ionic surfactant is the spanlastics, a novel elastic nanovesicle carrier. The drugs that are either lipophilic or hydrophilic can be administered via spanlastics. This nanocarrier system are enclosed in compartment composed of outer lipid and interior hydrophilic layers. These are vesicular carriers that are nontoxic, biodegradable, and nonimmunogenic. Several studies have shown that SPs can reduce side effects, increase therapeutic efficacy, improve medication absorption, and increase patient compliance. These vesicular vehicles also perform better in terms of chemical stability than liposomes due to their flexibility, and they have other benefits across niosomal colloidal delivery systems. Additionally, by functioning as a disruptive agent and enhancing deformability against biological membranes, edge activator residency in the vesicle lipid membrane increases the permeability of nano-sized vesicles, both of which are acknowledged advantages of spanlastic vesicles elasticity.3

This drug delivery innovation is part of a continuous evolution and has less side effects than earlier approaches. As a kind of elastic nanovesicle, spanlastics may transport a variety of drug molecules, including hydrophobic and hydrophilic ones, making them a promising option for use as a drug delivery vehicle. Spanlastics interest in a variety of administrative methods has been increasing over time. One innovative type of vesicular carrier that can serve as a site-specific medication delivery method is SPs. These devices have the ability to deliver drugs to a wide range of target locations, including the skin, nose, mouth, and eye respectively. Simply by prevents degradation it from a biological environment, spanlastics increase the bioavailability of drug, at the site. Spanlastics are stable, osmotically active, and capable of entrapping solutes. Because of its adaptable structural feature, they can be altered to meet the required standards.3

MAIN FEATURES OF SPANLASTICS4

1. Osmotically active and stable solutes can be entrapped by the spanlastics.

2. Spanlastic bilayer structure which supports the arrival of encased medication and allows them to in a controlled release drug delivery.

3. Because of their structural characteristic’s flexibility, they can be modified to achieve required standards.

4. By encapsulating the drug from biological environment, spanlastics improve the drug availability at the site.

ADVANTAGES4,5

1. Hydrophilic or lipophilic drug can be easily penetrating the biological membrane,such as cornea by the spanlastics.

2. Spanlastics are prepare to achieve the site-specific action.

3. These elastic vesicle features enable them to pass through the corneal membrane, vitreous cavity, and choroid in both the anterior and posterior portions of the eye, targeting the retinal pigment epithelium.

4. Spanlastics are naturally biodegradable and do not trigger the immunological response.

5. Spanlastics compared to traditional method, have more bioavailability because the drug features protective support, which allows it to reach the intended site without being degradation.

6. They continue to produce osmotic activity and the stability of API after it has been encapsulated.

7. These postpone the elimination of molecules of medicament from the systemic circulation during prolonged drug administration.

8. By encasing the drug in a lipid bilayer structure, they protect it from the harsh conditions of the biological environment.

9. They can be administered through oral, parenteral and even topical.

10. There are no any special requirements for handling or storing surfactant.

11. Compared to the liposomes, spanlastics are more chemically stable.

12. Method of preparation of spanlastics are economic and reliable.

DISADVANTAGES5,6

1. It has a poor water solubility.

2. it is easily degraded in an environment similar to that of the stomach, which is acidic. This makes it susceptible to first-pass metabolism in the liver.

3. Extrusion and sonication are the most common methods for preparing MLV, both take a significant amount of time and frequently necessitate the use of specialist machinery.

CLASSIFICATION OF SPANLASTICS

It is categorized according to the number of layers that it is composed of (Similarly to liposomes; SPs also can be categorized based on the numbers of layers it contain), which are discussed as below.7,8,9

1. Small Unilamellar Vesicles (SUVs): In general, the size of SUVs is between 10- 100nm. These are prepared through sonication method.

2. Multi-Lamellar Vesicles (MLVs): MLVs size approx. is 500- 1000nm in diameter. These are commonly used, easy to prepare a stable for a long duration.

3. Large Unilamellar Vesicles (LUVs): LUVs size range between 100- 3000nm. LUVs can entrap large amount of API.

Table 2. Classification of spanlastics

SR. NO.	TYPES OF SPs	SIZE
1.	SUVs	10 - 100nm
2.	MUVs	500 - 1000nm
3.	LUVs	100 - 3000nm

COMPOSITIONS OF SPANLASTICS

1. Nonionic Surfactant

Non-ionic surfactants are commonly used as wetting agents while creating vesicles because to their numerous benefits. Compared to anionic, amphoteric and cationic surfactants, they are more stable, compatible, and less harmful. Non-ionic surfactants exhibit strong interfacial activity due to their polar and non-polar components.14 The critical packing parameter (CPP), the chemical makeup of the ingredients, and the HLB of the wetting agent are some of the variables that may affect the formation of bilayer vesicles.Vesicles based on span 40 (HLB 6.7) and span 60 (HLB 4.7) are more stable and less likely to be disturbed, aggregated, and unstable compared to those based on span 80. Span 60's lipophilic qualities enable it to create lamellar matrix vesicles and entrap medicines more effectively than other non-ionic surfactants.10-12

2. Edge Activator

Edge activators are a unique type of hydrophilic or higher HLB value surfactant. These are single chain surfactants that reduce interfacial tension of the bilayer vesicles, destabilizing them and making them more deformable. Thus, they give these vesicles, lipid bilayer membranes flexibility. Edge activators typically form more spherical vesicles, which results in lower particle sizes.Combining an edge activator with SPs improves flexibility and reduces interfacial tension, allowing large particles to easily move through microscopic pore.13-15

3. Ethanol

The addition of ethanol improves the characteristics of these micro vesicular carrier. It is beneficial because it can condense membranes. It makes easier for the medication to divide and entrap inside the vesicles. By decreasing the thickness of vesicular membrane, the spanlastic system ability to entrap the drugs is increased.16-19

REMARKABLE CHARACTERISTICS OF SPANLASTICS

SPs are biodegradable, non-immunogenic, constantly release drugs, have flexible vesicles that enable them to pass across biological membranes with ease and without harm, and they also aid in increasing patient adherence. Because SPs contain non-ionic surfactants, they are non-irritating and can carry both hydrophilic and hydrophobic drugs. Because SPs are versatile delivery vehicles, they can be used as specialized pharmaceutical delivery systems.20- 22

MECHANISM OF PANETRATION OF SPANLASTICS

Edge activators (EAs) work by disrupting the lipid bilayers in vesicles, making them more flexible and adaptable. The surfactants in these vesicles create small openings in lipid membranes, and at higher amounts, can even break down (lyse) these membranes. This flexibility allows the elastic vesicles to gently squeeze through the tiny spaces between cells, especially when a water gradient is present that helps drive this movement. The exact behavior depends on the properties of the membrane they are interacting with.23, 24 Figure.1

There are 2 mechanisms for drug penetration as seen in below figure.

I. The elastic vesicles change the intercellular lipid lamellae by interacting with the epithelial cell membrane and functioning as penetration enhancers.

II. The elastic vesicles can work as drug-carrier systems, allowing the vesicles interact with medication to travel beyond the biological membrane and through intercellular gaps. Two factors contribute towards successful passage of these carriers:

1. The vesicle bilayers extremely stress-dependent flexibility

2. An osmotic gradient is present.

FIG.1 MECHANISM OF SPANLASTICS PANETRATION INSIDE THE EPIDERMIS AND LIPID BILAYER

METHODS OF PREPARATION

1. Ethanol injection method: This process involves mixing an edge activator with a fixed amount of non-ionic surface active agent to create spanlastics. The medication is initially dissolved in ethanol mixed with span to get it ready for encapsulation. 5 mins. are spent sonicating the lipid solution. The edge activator (such Tween-80) in a heated aqueous phase is now continuously injected with this solution. For the last half hour, this phase has been agitated on a magnetic stirrer at temperatures between 70 and 80 degrees Celsius and speeds between 800 and 1600 rpm.25 FIG. 2

FIG.2 Ethanol injection method

2. Hand shaking method: First of all dissolve surfactant in an organic solvent, then the solvent is vaporized in a vaccum evaporator fitted with a round-bottom flask, where pressure is gradually decreased, and the layer is re-hydrated using an aqueous solution containing the prescribed drugs, followed by constant agitation, which causes the surfactant layer to thicken. Amphiphilic molecules that have swelled will eventually fold, creating vesicles that act as encapsulating structures for the medication.26

3. Sonication: This process involves creating an aliquot of the drug in a buffer and adding it to the mixture of surfactants in a glass vial that holds 10 millilitres. The mixture is sonicated using the titanium probe.27

4. Ether injection: A 14-gauze needle is used to inject the surfactant into an aqueous phase that has been heated to 600 degrees Celsius at a rate of 25 milliliters per minute. The surfactant must be dissolved in 20 milliliters of ether in order to use this procedure. A rotary evaporator will be used to remove the ethanol from the ether solution. Vesicles with a single layer will occur as a result of the procedure once the organic solvent has been totally eliminated.28

5. Thin film hydration technique: Following a thorough weighing process, span 60 will be moved to a round-base flask and mixed in the chloroform. A thin coating will develop on the flask walls as the organic solvent is vacuum-evaporated at 55 degrees Celsius through a rotary evaporator spinning at ninety revolutions per minute. A specified amount of the medication can be dissolved in the aqueous phase by the chosen EA and co-solvent. After the thin film has been deposited, this aqueous phase will be added. To completely remove the lipid coating from the flask's walls, it will be rotated for 30 minutes at 60 degrees Celsius, normal pressure, and 90 revolutions per minute after being reattached to the evaporator. After standing for two more hours at room temperature to fully hydrate, the resulting distribution will be kept at 4 degrees Celsius overnight.29

6. Microfluidization method: In the interaction chamber, two fluidized streams, one holding the medication and other containing the surfactant, reach at high speeds via microchannels. The submerged jet technique assures that energy remains inside the spanlastic formulation zone. The formulation has increased homogeneity, reduced size, and improved reproducibility.30

EVALUATIONS OF SPANLASTICS

1. Entrapment Efficiency (EE):

Combining a precise amount of SPs dispersion with a suitable solvent volume allowed for quantification of drug content, including both unentrapped and entrapped levels. Next, the drug content is analyzed using spectrophotometry. Entrapment efficiency refers to the proportion of drug contained within the SP and can be calculated using the method indicated below (12).

To assess entrapment efficiency, any substance not trapped by SPs is removed using centrifugation techniques. The residual solution is separated out, and the supernatant is obtained. The liquid is collected, diluted to a specific concentration, and tested using the technique specified in the drug monograph. The yield and efficiency of SP entrapment depend on the medication's physicochemical properties and production process.31, 32

2. Transmission Electron Microscopy (TEM):

TEM is used to assess the size, shape and lamellarity of SPs. To speed up the procedure, create a suspension and add 1% phosphotungstic acid. After draining excess liquid, the mixture is placed on a carbon-covered grid and allowed to dry entirely. The grid is shot at the appropriate magnification using a TEM.33, 34

3. Freeze Fractured Microscopy:

Drug entrapment, drug type, and surfactant all affect SP size and shape. Vesicles are freeze-thawed and inspected using a freeze-cracked electron microscope to measure their size. Vesicular suspensions are frequently frozen at low pressure (10_2 Pa) using liquid propane. Another application for glycol is as a cryoprotectant. At a particular angle, the cryofixed vesicles break. Then, at a 45-degree angle, platinum or carbon vapors cast a shadow on the surface. Carbon coating is used in this technology to strengthen the duplicate. TEM is used to clean and examine the replica.35, 36

4. Optical Microscopy Technique:

This approach is also used to assess size and shape. About 100 SPs are employed to determine particle size. This approach involves measuring the stage and eyepiece micrometers, then calculating the formulation size. Laser beam-based mastersizers are commonly used to find out the size, mean surface diameter, and mass distribution of spanlastics. DLS analysis using the Malvern zeta sizer is used to examine size distribution, mean diameter, and zeta potential. 37, 38

5. Elasticity Measurement:

The vesicles were expelled with a polycarbonate filter with 50 nm wide holes and continuous pressure. The procedure entailed using a 200 ml barrel and a stainless steel pressure holder with a 25mm filter. The intervals before and after the extrusion technique influenced the particle size of the extruded suspension. SPs flexibility allows it to slip past the mucus barrier, making it a unique vesicle type.39, 40

6. Stability Study:

This experiment assess pharmaceutical leakage from vesicles while in storage. The drug's preservation ability is tested by storing the chosen elastic vesicular suspension in glass vials at 480C for three months. Periodically, samples are extracted and analyzed for drug permeation, entrapment, and residual content.40

7. In-vitro Release Study:

This trial showed that the dialysis membrane technique was the most effective. SPs were added in a precise amount to the dialysis bag. To mix the dissolving liquid and dialysis bag, use a magnetic stirrer at 37°C. At regular intervals, fresh dissolving medium was introduced to the beaker while a sample solution was removed. The samples were examined spectrophotometrically to determine the maximal drug concentration.41, 42

8. In-vivo Study:

In vivo studies were performed using albino rats as experimental models. Bhaskaran and Lakshmi employed three groups of healthy rats, each weighing between 100–150 gm. and comprising three animals. The 1st group served as the control and was administered blank spanlastic vesicles without the drug. The 2nd group received the free drug, while the third group was treated with the drug-loaded formulation. Following treatment, the animals were sacrificed, and major organs such as the liver, lungs, spleen, kidneys, and heart were excised. These tissues were rinsed with phosphate buffer (pH 7.4), homogenized, and subjected to centrifugation. The resulting supernatant was subsequently analyzed to determine the drug concentration using an appropriate analytical method. Similarly, Jadon et al. investigated tissue and plasma drug distribution in male albino rats. Three groups of five rats each were created from the animals. The pure drug was given to the second group, while phosphate-buffered saline (PBS, pH 7.4) was given to the first group, which was the control. The drug was administered orally to the third group using nanovesicular formulations. At predetermined time intervals, blood samples were collected, centrifuged, and immediately frozen. Drug levels in plasma were then quantified through high-performance liquid chromatography (HPLC).43- 45

ADVANCED CLINICAL APPLICATIONS OF SPANLASTICS IN TARGETED DRUG DELIVERY BEYOND CURRENT EXPERIMENTAL STAGES-

Surfactant	Edge Activator	Method of Formulation	Entrapment Efficacy (%)	Route of Administration	Drug Loaded	Application/ Indication	References
Span 60	Tween 60	Ethanol injection	Up to 85	Oral/Buccal/Sublingual	Famotidine	Ulcers, gastroprotection	?46
Span 60	SDC	Ethanol Injection+Sonication	80.4	Intranasal	Flibanserin	Female sexual disorder, CNS	?47
Span 60	Tween 80	Ethanol injection	66–77	Transdermal	Tacrolimus	Skin disorders, immunosuppression	?48
Span 60	Tween 80	Thin film hydration	72–90	Ocular	Methazolamide	Glaucoma	?49
Span 60	Tween 60/Tween 80	Thin film hydration	78–90	Transdermal	Glimepiride	Diabetes mellitus	?50
Span 60	Tween 80	Ethanol injection	60–82	Topical	Fenoprofen calcium	Arthritis—sustained anti-inflammatory effect	?51
Span 60	Tween 80	Modified spraying	70–85	Intranasal	Rasagiline mesylate	CNS, Parkinson’s disease	?52
Span 60	Tween 80	Ethanol injection	75–93	Transungual	Efinaconazole	Nail fungal infection	?53
Span 60	Tween 80	Ethanol injection	72–85	Oral/Buccal	Carvedilol	Cardiovascular disorders	?54
Span 60	SDC/Tween 60	Ethanol injection	80–88	Ocular	Fluconazole	Ocular mycoses	?55
Span 60	Tween 80	Ethanol injection	80–90	Topical	L-ascorbic acid	Antioxidant skin, UV protection	?56
Span 60	Tween 80	Thin film hydration	85–88	Topical	Thymoquinone	Anticancer (breast cancer)	?57
Span 60	Tween 80	Sonication	82–90	Topical/transdermal	Fluvastatin sodium	Rheumatoid arthritis	?58
Span 60	Tween 80/SDC/Tween 60	Ethanol injection	70–90	Ocular	Itraconazole	Fungal infections	?59
Span 60	SDC/Tween 80	Ethanol injection	73–88	Transdermal	Haloperidol	Psychosis, CNS	?60

SPANLASTICS IN HERBAL MEDICINE

Spanlastics offer a smart way to boost the effectiveness of herbal medicines by packaging plant-based compounds into flexible, tiny vesicles that improve absorption and stability.61,62

1. Why Use Them for Herbs?

Herbal actives like curcumin or silymarin often face issues such as poor solubility, quick breakdown, or low absorption, limiting their real-world benefits. Spanlastics protect these compounds, enhance skin or nasal penetration, and allow steady release, potentially cutting down doses while maximizing effects.63-64

2. Real World Examples

Researchers loaded curcumin from turmeric into spanlastics for a topical anti-aging gel, achieving better skin penetration and results than standard creams. Similarly, green tea's EGCG saw improved bioavailability in nanospanlastic form, showing promise for antioxidants.65,66

3. Pros and Challenges

They stand out for better stability, no immune reactions, and versatility across delivery routes like skin or nose. Still, scaling up production, ensuring long-term shelf life with herbs, and running more human trials remain hurdles before widespread use.67,69

TOXICOLOGICAL SAFETY OF SPANLASTICS

1. Concern About Surfactant

Non-ionic surfactants such as Span and Tween are generally regarded as safe (GRAS), yet their concentration and frequency of exposure can induce irritation, compromise barrier integrity, and exhibit cytotoxicity. Experimental spanlastic formulations frequently incorporate elevated surfactant levels to optimize vesicular elasticity, rendering them potentially unsuitable for chronic topical or mucosal applications absent comprehensive toxicological validation. While numerous ex vivo and in vivo investigations demonstrate negligible irritation or histopathological alterations at tested concentrations, these assessments are predominantly short-duration and rodent-based, underscoring uncertainties regarding cumulative toxicity, sensitization potential, and microbiome perturbations in human subjects.70-73

2. Long Term and Mucosal Contact

Spanlastics are designed to deform and penetrate deeply through the stratum corneum or mucosal epithelium, raising the possibility of higher local and even systemic exposure to both surfactants and entrapped drugs over time. For chronic indications (e.g., anti aging, psoriasis, nasal delivery for CNS drugs), long duration application could theoretically alter skin barrier integrity, mucociliary clearance, or local immune responses, yet systematic chronic toxicity and sensitization studies are largely lacking. These concerns become more relevant when spanlastics are combined with potent actives (NSAIDs, immunomodulators, CNS drugs), where enhanced penetration may amplify both therapeutic effect and adverse reactions.74-77

3. Gaps In Vivo and Clinical Evidence

Most spanlastic research stops at in vitro characterization, ex vivo permeation, and short term animal studies, with very few reports extending into formal pharmacokinetics, long term safety, or human clinical trials. Data on reproductive toxicity, genotoxicity, immunotoxicity, and chronic dermal or mucosal exposure are minimal, and almost no controlled clinical studies directly compare spanlastic products to established marketed nanocarriers such as liposomes or niosomes. This evidence gap makes it difficult for regulators to fully assess benefit–risk balance and hinders translation into registered, labeled products despite strong preclinical performance.78-81

4. Requirement of Market Translation

To move spanlastics from bench to market, developers will need systematic toxicology packages aligned with ICH and regional nanomedicine guidelines, including dose ranging repeat dose in vivo studies, local tolerance tests, and, for chronic use, long term dermal or mucosal safety evaluations. Well designed early phase clinical trials should document irritation, sensitization, systemic exposure, and comparative safety versus conventional formulations, while quality by design approaches must ensure consistent vesicle size, surfactant content, and impurity profiles across scale up.81-83

CURRENT DEVELOPMENT AND MARKET STATUS OF SPANLASTICS

Research has explored spanlastic gels, patches, and in situ gels for drugs like celecoxib, tacrolimus, levofloxacin, felodipine, and zaleplon, mainly as lab scale or preclinical formulations. However, literature and reviews indicate that clearly identified, widely marketed finished products based specifically on “spanlastics” are not yet established, so the system should be viewed as an innovative platform under active development rather than a fully commercialized technology.84-86

CONCLUSION

Spanlastics are emerging as an innovative vesicular drug delivery system that offers a non-invasive way to transport medications directly to the desired site in the body. They help overcome common pharmaceutical challenges such as poor solubility, instability, low bioavailability, and rapid degradation of drugs. Because of these properties, spanlastics are gaining attention as a potential breakthrough in nanovesicular delivery technology. They can carry both water-loving (hydrophilic) and fat-loving (lipophilic) drugs, ensuring more precise, site-specific therapeutic effects. Currently, this system is being explored for delivering treatments through various routes, including ocular, oral, topical, nasal, trans-ungual, and even to the middle ear.

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Sallam NM, Sanad RAB, Ahmed MM, Khafagy ELS, Ghorab M, Gad S. Impact of the mucoadhesive lyophilized wafer loaded with novel carvedilol nano-spanlastics on biochemical markers in the heart of spontaneously hypertensive rat models. Drug Deliv Transl Res. 2021 Jun;11(3):1009-1036. doi: 10.1007/s13346-020-00814-4. PMID: 32607938.
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Elhabak M, Ibrahim S, Abouelatta SM. Topical delivery of l-ascorbic acid spanlastics for stability enhancement and treatment of UVB induced damaged skin. Drug Deliv. 2021 Dec;28(1):445-453. doi: 10.1080/10717544.2021.1886377. PMID: 33620008; PMCID: PMC7909477.
Alaaeldin, E., Mostafa, M., Mansour, H. F., & Soliman, G. M. (2021). Spanlastics as an efficient delivery system for the enhancement of thymoquinone anticancer efficacy: Fabrication and cytotoxic studies against breast cancer cell lines. Journal of Drug Delivery Science and Technology, 65, 102725. https://doi.org/10.1016/j.jddst.2021.102725.
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Kumar L., Rana R., Kukreti G., Aggarwal V., Chaurasia H., Sharma P., Jyothiraditya V. Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes // Current Pharmaceutical Design. - 2024. - Vol. 30. - N. 28. - P. 2206-2221. doi: 10.2174/0113816128313398240613063019.
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El Hosary R, Teaima MH, El-Nabarawi M, Yousry Y, Eltahan M, Bakr A, Aboelela H, Abdelmonem R, Nassif RM. Topical delivery of extracted curcumin as curcumin loaded spanlastics anti-aging gel: Optimization using experimental design and ex-vivo evaluation. Saudi Pharm J. 2024 Jan;32(1):101912. doi: 10.1016/j.jsps.2023.101912. Epub 2023 Dec 9. PMID: 38178851; PMCID: PMC10765109.
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Kumar L., Rana R., Kukreti G., Aggarwal V., Chaurasia H., Sharma P., Jyothiraditya V. Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes // Current Pharmaceutical Design. - 2024. - Vol. 30. - N. 28. - P. 2206-2221. doi: 10.2174/0113816128313398240613063019.
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Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.
Elhabak M, Ibrahim S, Abouelatta SM. Topical delivery of l-ascorbic acid spanlastics for stability enhancement and treatment of UVB induced damaged skin. Drug Deliv. 2021 Dec;28(1):445-453. doi: 10.1080/10717544.2021.1886377. PMID: 33620008; PMCID: PMC7909477.
Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
Annisa, R. (2025c). Spanlastic as a Transdermal Drug Delivery System: A Systematic review. Biomedical & Pharmacology Journal, 18(1), 447–457. https://doi.org/10.13005/bpj/3099.
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Alaaeldin E, Abou-Taleb HA, Mohamad SA, Elrehany M, Gaber SS, Mansour HF. Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Down-Regulation of TNF-α, NF-?B and COX-2 in Complete Freund’s Adjuvant-Induced Arthritis Model in Rats. Int J Nanomedicine. 2021;16:133-145

https://doi.org/10.2147/IJN.S289828.

Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.
Badria F, Mazyed E. Formulation of Nanospanlastics as a Promising Approach for ‎Improving the Topical Delivery of a Natural Leukotriene Inhibitor (3-‎Acetyl-11-Keto-β-Boswellic Acid): Statistical Optimization, in vitro ‎Characterization, and ex vivo Permeation Study. Drug Des Devel Ther. 2020 Sep 15;14:3697-3721. doi: 10.2147/DDDT.S265167. PMID: 32982176; PMCID: PMC7501970.
Kumar, L., Rana, R., Kukreti, G., Aggarwal, V., Chaurasia, H., Sharma, P., & Jyothiraditya, V. (2024). Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes. Current Pharmaceutical Design, 30(28), 2206–2221. https://doi.org/10.2174/0113816128313398240613063019.
Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.
Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
El-Shenawy AA, Abd Elkarim RA, Mahmoud RA, Ramadan AEH, Alamri AH, Abdelkader H, Elafify MS, Mahmoud EA, Saddik MS, Mohamed MS. Zaleplon nanospanlastics loaded transdermal patches: formulation, optimization, ex-vivo permeation, and in-vivo studies. J Pharm Pharm Sci. 2025 Nov 5;28:15406. doi: 10.3389/jpps.2025.15406. PMID: 41268063; PMCID: PMC12626903.
Alaaeldin E, Abou-Taleb HA, Mohamad SA, Elrehany M, Gaber SS, Mansour HF. Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Down-Regulation of TNF-α, NF-?B and COX-2 in Complete Freund’s Adjuvant-Induced Arthritis Model in Rats. Int J Nanomedicine. 2021;16:133-145

https://doi.org/10.2147/IJN.S289828

Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.

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https://doi.org/10.2147/IJN.S289828.

Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.
Badria F, Mazyed E. Formulation of Nanospanlastics as a Promising Approach for ‎Improving the Topical Delivery of a Natural Leukotriene Inhibitor (3-‎Acetyl-11-Keto-β-Boswellic Acid): Statistical Optimization, in vitro ‎Characterization, and ex vivo Permeation Study. Drug Des Devel Ther. 2020 Sep 15;14:3697-3721. doi: 10.2147/DDDT.S265167. PMID: 32982176; PMCID: PMC7501970.
Kumar, L., Rana, R., Kukreti, G., Aggarwal, V., Chaurasia, H., Sharma, P., & Jyothiraditya, V. (2024). Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes. Current Pharmaceutical Design, 30(28), 2206–2221. https://doi.org/10.2174/0113816128313398240613063019.
Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.
Almohamady HI, Mortagi Y, Gad S, Zaitone S, Alshaman R, Alattar A, Alanazi FE, Hanna PA. Spanlastic Nano-Vesicles: A Novel Approach to Improve the Dissolution, Bioavailability, and Pharmacokinetic Behavior of Famotidine. Pharmaceuticals (Basel). 2024 Nov 29;17(12):1614. doi: 10.3390/ph17121614. PMID: 39770456; PMCID: PMC11678360.
El-Shenawy AA, Abd Elkarim RA, Mahmoud RA, Ramadan AEH, Alamri AH, Abdelkader H, Elafify MS, Mahmoud EA, Saddik MS, Mohamed MS. Zaleplon nanospanlastics loaded transdermal patches: formulation, optimization, ex-vivo permeation, and in-vivo studies. J Pharm Pharm Sci. 2025 Nov 5;28:15406. doi: 10.3389/jpps.2025.15406. PMID: 41268063; PMCID: PMC12626903.
Alaaeldin E, Abou-Taleb HA, Mohamad SA, Elrehany M, Gaber SS, Mansour HF. Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Down-Regulation of TNF-α, NF-?B and COX-2 in Complete Freund’s Adjuvant-Induced Arthritis Model in Rats. Int J Nanomedicine. 2021;16:133-145

https://doi.org/10.2147/IJN.S289828

Agha OA, Girgis GNS, El-Sokkary MMA, Soliman OAE. Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study. Int J Pharm X. 2023 Jul 24;6:100201. doi: 10.1016/j.ijpx.2023.100201. PMID: 37560488; PMCID: PMC10407905.

Keshav Maurya

Corresponding author

Department of Pharmacy, Mahatma Jyotiba Phule Rohilkhand University Bareilly 243006 U.P. India

Sobhna Singh

Co-author

Department of Pharmacy, Mahatma Jyotiba Phule Rohilkhand University Bareilly 243001, Uttar Pradesh, India.

Neha

Co-author

Department of Pharmacy, Mahatma Jyotiba Phule Rohilkhand University Bareilly 243001, Uttar Pradesh, India.

Keshav Maurya, Sobhna Singh, Neha, Revolutionizing Drug Delivery: Spanlastics as Adaptive Nanovesicular Platforms for Multimodal Therapeutics, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 4, 4862-4879, https://doi.org/10.5281/zenodo.19909752

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Revolutionizing Drug Delivery: Spanlastics as Adaptive Nanovesicular Platforms for Multimodal Therapeutics

Abstract

Keywords

Introduction

Reference

Keshav Maurya

Sobhna Singh

Neha

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