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In the dynamic landscape of pharmaceutical advancements, the strategic application of active pharmaceutical ingredients to the skin through topical and transdermal routes has emerged as a compelling avenue for therapeutic interventions. This non-invasive approach has garnered considerable attention in recent decades, with numerous attempts yielding approaches and demonstrating substantial clinical potential. However, the formidable barrier function of the skin, mainly the confinement of drugs on the upper layers of the stratum corneum, poses a substantial hurdle, impeding successful drug delivery via this route. Ultradeformable vesicles/carriers (UDVs), positioned within the expansive realm of nanomedicine, have emerged as a promising tool for developing advanced dermal and transdermal therapies. The current review focuses on improving the passive dermal and transdermal targeting capacity by integrating functionalization groups by strategic surface modification of drug-loaded UDV nanocarriers. The present review discusses the details of case studies of different surface-modified UDVs with their bonding strategies and covers the recent patents and clinical trials. The design of surface modifications holds promise for overcoming existing challenges in drug delivery by marking a significant leap forward in the field of pharmaceutical sciences. [ABSTRACT FROM AUTHOR]

Abstract Background Boswellic acid (BA), a phytoconstituent obtained from Boswellia serrata, suffers from several limitations after oral administration such as poor systemic absorption, high first-pass metabolism and high frequency of dose requirement, which creates a need to develop an alternative route for drug administration via novel drug delivery formulation. The present research work aims at developing ultradeformable vesicular carriers (transferosomes) for transdermal delivery of boswellic acid to effectively deliver the drug into deeper layers of the skin reaching the target site and thus improving its systemic bioavailability. Ultradeformable vesicles were prepared by thin-film hydration technique, and the formulation was optimized using 32 full factorial design where the amount of lecithin (mg) and concentration of surfactant (%) were considered as independent variables. The formulated boswellic acid-loaded vesicles were incorporated into transdermal film via solvent evaporation technique using the blend of polymers such as starch and HPMC K4M. Results The BA-loaded transferosomes were optimized based on vesicle size (nm) and drug entrapment efficiency (%EE), and the results were found to be 205.4 ± 1.215 nm and 86.39 ± 0.019%, respectively. Transmission electron microscopy (TEM) of optimized batch showed spherical shape of vesicles with identified lamellarity, surface charge of vesicles with high negative value − 15.2 mV that suggests electrostatic repulsion between vesicles, while the formulation showed good deformability index of 11.31 ± 0.032% due to use of Tween 80 as surfactant. In vitro permeation study demonstrated sustained release pattern of 96.53 ± 0.023% up to 24 h. Also, the in vitro drug diffusion study was carried out for transfersomal transdermal film which exhibited enhanced permeation and sustained retention of drug up to 94.71 ± 0.019% for 24 h. Conclusion Accordingly, the research work suggested that the transferosomes provided an efficient nanosized carriers for enhanced permeation of boswellic acid into deeper layers of skin and could successfully exhibit its therapeutic effect.

The emergence of lipid nanovesicles (LNVs), like liposomes, transferosomes, and ethosomes, strengthens transdermal drug delivery. The composition of lipid vesicles is similar to that of skin, so these can easily penetrate through the skin. Modifications in the design of lipid vesicles help enhance skin permeation; therefore, dose reduction is possible. Ultradeformable vesicles are superior to conventional lipid vesicles because of their better stability. Various methods used to prepare LNVs are the classical cold method, ethanol injection method, ether injection method, and film hydration method. The method of preparation is crucial because it drastically affects the characteristics of vesicles. The vesicles are evaluated for their physicochemical and biological properties. Since vesicular systems are more susceptible to physical, chemical, and biological degradation, their stability is critical and challenging. The transdermal applications of LNVs spread across all areas like antifungal, anti-inflammatory, and anticancer drugs and the delivery of proteins and peptides. [ABSTRACT FROM AUTHOR]

Objective: Aim of the present work was to optimize and formulate resveratrol loaded vesicular cream intended for dermal delivery of resveratrol with high skin deposition potential. Methods: Formulation was developed and optimized using Central Composite Design. Amount of phospholipid and sodium cholate were selected as critical material attributes and vesicle size and entrapment efficiency of resveratrol were taken as critical quality attributes. To increase the skin applicability and patient compliance, vesicles were further developed as vesicular cream which was then thoroughly characterized for physicochemical parameters, ex vivo skin permeation/deposition profile and antioxidant potential. Results: Vesicle size and entrapment efficiency of the optimized batch were found to be 178.9 ± 12.87 nm with 72.32 ± 3.45% respectively. Physicochemical properties and viscosity of cream formulation were also found to be favorable for skin applicability. Permeation flux at the end of 24 h was found to be 2.70 ± 0.73, 4.45 ± 0.56 and 4.95 ± 0.69 µg cm−2h−1 for conventional cream, vesicular dispersion, and vesicular cream formulation respectively. Higher drug deposition in the skin via vesicular cream formulation was observed i.e. 335.2 ± 4.12 µg cm−2 (70.16 ± 0.87%) as compared to conventional cream i.e. 67.12 ± 19.63 µg cm−2 (14.05 ± 4.11%). Resveratrol encapsulated in vesicular cream has retained its inherent antioxidant activity suggesting the stability of resveratrol in vesicular cream. Conclusion: Thus, it can be concluded that deformable vesicular cream is capable of delivering encapsulated bioactive in deeper layers of skin, where it can be retained for achieving higher dermatological benefits. [ABSTRACT FROM AUTHOR]

Gene therapy is a revolutionary approach aimed at treating various diseases by manipulating the expression of specific genes. The composition and formulation of ultra-deformable vesicles play a crucial role in determining their properties and performance as siRNA delivery vectors. In the development of ultra-deformable vesicles for siRNA delivery, careful lipid selection and optimization are crucial for achieving desirable vesicle characteristics and efficient siRNA encapsulation and delivery. The stratum corneum acts as a protective barrier, limiting the penetration of molecules, including siRNA, into the deeper layers of the skin. Ultradeformable vesicles offer a promising solution to overcome this barrier and facilitate efficient siRNA delivery to target cells in the skin. The stratum corneum, the outermost layer of the skin, acts as a significant barrier to the penetration of siRNA.These engineering approaches enable the production of uniform and well-defined vesicles with enhanced deformability and improved siRNA encapsulation efficiency. Looking ahead, advancements in ultra-deformable vesicle design and optimization, along with continued exploration of combination strategies and regulatory frameworks, will further drive the field of ultra-deformable vesicle-based siRNA delivery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Graphical abstract Highlights • Baicalin or berberine were encapsulated in ultradeformable vesicles. • Antioxidant and photoprotective effects of ultradeformable vesicles were confirmed. • Ultradeformable vesicles had a great potential as stimulant of pigmentation. • Promising formulations for the treatment of vitiligo symptoms were developed. Abstract 0.5–1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distribution, surface charge and entrapment efficiency were assessed. The ability of the vesicles to promote the permeation of the polyphenols was evaluated. The antioxidant and photoprotective effects were investigated in vitro using keratinocytes and fibroblasts. Further, the stimulation of melanin production and tyrosinase activity in melanocytes after treatment with the vesicles were assessed. Ultradeformable vesicles were small in size, homogeneously dispersed, and negatively charged. They were able to incorporate high amounts of baicalin and berberine, and promote their skin permeation. In fact, the polyphenols concentration in the epidermis was higher than 10%, which could be indicative of the formation of a depot in the epidermis. The vesicles showed remarkable antioxidant and photoprotective capabilities, presumably correlated with the stimulation of melanin production and tyrosinase activity. In conclusion, baicalin or berberine ultradeformable vesicles, and particularly their combination, may represent promising nanosystem-based adjuvants for the treatment of vitiligo symptoms. [ABSTRACT FROM AUTHOR]

The topical efficacy of baicalin, a natural flavonoid isolated from Scutellaria baicalensis Georgi , which has several beneficial properties, such as antioxidative, antiviral, anti-inflammatory and antiproliferative, is hindered by its poor aqueous solubility and low skin permeability. Therefore, its incorporation into appropriate phospholipid vesicles could be a useful tool to improve its local activity. To this purpose, baicalin at increasing concentrations up to saturation, was incorporated in ultradeformable vesicles, which were small in size (∼67 nm), monodispersed (PI < 0.19) and biocompatible, regardless of the concentration of baicalin, as confirmed by in vitro studies using fibroblasts. On the other hand, transdermal flux through human epidermis was concentration dependent. The in vivo results showed the significant anti-inflammatory activity of baicalin loaded nanovesicles irrespective of the concentration used, as they were able to reduce the skin damage induced by the phorbol ester (TPA) application, even in comparison with dexamethasone, a synthetic drug with anti-inflammatory properties. Overall results indicate that ultradeformable vesicles are promising nanosystems for the improvement of cutaneous delivery of baicalin in the treatment of skin inflammation. [ABSTRACT FROM AUTHOR]

1-(1-Naphthyl)piperazine (1-NPZ) has shown promising effects by inhibiting UV radiation-induced immunosuppression. Ultradeformable vesicles are recent advantageous systems capable of improving the (trans)dermal drug delivery. The aim of this study was to investigate 1-NPZ-loaded transethosomes (NPZ-TE) and 1-NPZ-loaded vesicles containing dimethyl sulfoxide (NPZ-DM) as novel delivery nanosystems, and to uncover their chemopreventive effect against UV-induced acute inflammation. Their physicochemical properties were evaluated as follows: vesicles size and zeta potential by dynamic and electrophoretic light scattering, respectively; vesicle deformability by pressure driven transport; rheological behavior by measuring viscosity and I-NPZ entrapment yield by HPLC. In vitro topical delivery studies were performed in order to evaluate the permeation profile of both formulations, whereas in vivo studies sought to assess the photoprotective effect of the selected formulation on irradiated hairless mice by measuring myeloperoxidase activity and the secretion of proinflammatory cytokines. Either NPZ-TE or NPZ-DM exhibited positive results in terms of physicochemical properties. In vitro data revealed an improved permeation of 1-NPZ across pig ear skin, especially by NPZ-DM. In vivo studies demonstrated that NPZ-DM exposure was capable of preventing UVB-induced inflammation and blocking mediators of inflammation in mouse skin. The successful results here obtained encourage us to continue these studies for the management of inflammatory skin conditions that may lead to the development of skin cancers. [ABSTRACT FROM AUTHOR]

Aim: Present research work aimed to explore intravaginal route for the drug delivery for treatment of endometrial cancer (EC). Material & methods: Carboplatin (CBP)-loaded ultradeformable vesicle (CBP-UDV) was prepared and characterized for in vitro quality attributes and evaluated for its efficacy in rabbits using ultrasound imaging after intravaginal administration. Results & conclusion: The results showed that the formulation capable of carrying and localizing drug in uterus for prolonged period assisted by first uterine pass effect. Ultrasound imaging of the EC-induced rabbit model before and after treatment with CBP-UDV showed considerable regression in the EC tumor mass. The findings serve as the basis of successful utilization of the intravaginal route for management of EC by designing the formulation which can improve patient compliance.

Introduction Ultradeformable vesicles are highly promising tools to enhance the percutaneous transport of different drugs such as tretinoin across the skin barrier and also to increase the formulation stability at absorption site and reduce the drug induced irritation. Methods Topical delivery of tretinoin-loaded ultradeformable vesicles (tretinoin–UDV) was evaluated concerning different studies, such as: the release and permeation profiles (tape stripping); skin penetration (fluorescence analysis); induced electrical changes in skin barrier properties; cytotoxicity (Trypan Blue assay) and skin irritation in in vivo conditions (Draize test). The novel formulation performance was also compared to a commercial tretinoin formulation regarding in vivo studies. Results It was obtained a sustained and controlled drug release, as expected for UDV formulation. In addition, a dermal delivery was observed regarding the permeation study since it was not detected any drug amount in the receptor phase after 24 h. Nile Red–UDV stained intensively mostly in the stratum corneum , corroborating the tape stripping results. Tretinoin–UDV decreased skin resistance, suggesting its ability to induce skin barrier disruption. Finally, the formulation vehicle (empty UDV) and tretinoin–UDV were not toxic under in vitro and in vivo conditions, at least, at 5 × 10 −3 mg/mL and 0.5 mg/mL of tretinoin, respectively. Conclusion Tretinoin−UDV is a promising delivery system for tretinoin dermal delivery without promoting skin irritation (unlike other commercial formulations), which is quite advantageous for therapeutic purpose. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this experimental work were the incorporation and full characterization of the system Tretinoin-in-dimethyl-beta-cyclodextrin-in-ultradeformable vesicles (Tretinoin-CyD-UDV) and Tretinoin-in-ultradeformable vesicles (Tretinoin-UDV). Methods: The Tretinoin-CyD complex was prepared by kneading and the UDV by adding soybean phosphatidylcholine (SPC) to Tween® 80 followed by an appropriate volume of sodium phosphate buffer solution to make a 10%-20% lipid suspension. The resulting suspension was brought to the final mean vesicles size, of approximately 150 nm, by sequential filtration. The physicochemical characterization was based on: the evaluation of mean particle size and polydispersity index (PI) measured by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM) topographic imaging; zeta potential (ζ-potential) and the SPC concentration determined by Laser-Doppler anemometry and an enzymatic-colorimetric test, respectively. The quantification of the incorporated Tretinoin and its chemical stability (during preparation and storage) was assayed by a HPLC at 342 nm. Results: It was possible to obtain the system Tretinoin-CyD-UDV. The mean vesicle size was the most stable parameter during experiments time course. AFM showed that Tretinoin-CyD-UDV samples were very heterogeneous in size, having three distinct subpopulations, while Tretinoin-UDV samples had only one homogeneous size population. The results of the ζ-potential measurements have shown that vesicle surface charge was low, as expected, presenting negative values. The incorporation efficiency was high, and no significant differences between Tretinoin-CyD-UDV and Tretinoin-UDV were observed. However, only Tretinoin-UDV with 20% lipid concentration formulation remained chemically stable during the evaluation period. Conclusion: According to our results, Tretinoin-UDV with 20% lipid concentration seems to be a better approach than Tretinoin-CyD-UDV, attending to the higher chemical stability. [ABSTRACT FROM AUTHOR]

Tenoxicam is one of the potent non-steroidal anti-inflammatory drugs (NSAIDs), which is used clinically in the treatment of rheumatoid arthritis. Like other NSAIDs, Tenoxicam also suffers from the drawback of being associated with gastrointestinal side effects. Further, transdermal penetration of this drug is very poor, which circumvents the use of transdermal route. The main objective of this study is to exploit the concept of ultradeformable vesicles to increase the transport of Tenoxicam through transdermal route, and also to present it as a possible replacement for the oral NSAID therapy for rheumatoid arthritis. Three concentrations (5%, 15% and 25%) of three different surfactants (Tween-80, Span-80 and sodium desoxycholate) were used along with soya lecithin to prepare the ultradeformable vesicles. Among nine different types of vesicles, T3 vesicles (with 25% Tween-80) were found to have shown the smallest size (82.80 ± 0.74 nm), highest release in 24 h (98.01 ± 0.33%) and highest deformability (31.27 ± 0.28) and hence chosen for formulating into the gel. Among three different Carbopol® 934 concentrations (1%, 1.5% and 2%), G-2 with 1.5% carbopol was chosen as the final formulation. The formulation has shown almost twice the transdermal flux as compared to the gel with free Tenoxicam. Thein vivoperformance was also found to be significantly better than the oral Tenoxicam and marketed aceclofenac gel (Hifenac®). This study concluded that the gel containing Tenoxicam encapsulated in ultradeformable vesicles has a better prospective for the transdermal use to treat rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Abstract: The potentiality of ultradeformable vesicles as a possible topical delivery system for asiaticoside, a natural compound obtained from Centella asiatica was evaluated, because this compound exhibits collagen biosynthesis promoting activity. Ultradeformable vesicles were prepared by the extrusion technique; these vesicles were composed of Phospholipon 100® and different molar fractions of sodium cholate as the edge activator. The physicochemical properties of the ultradeformable vesicles were investigated through differential scanning calorimetry and light scattering techniques. The potential cyctotoxicity and biological activity of asiaticoside-loaded ultradeformable vesicles were evaluated on primary human dermal fibroblast cells by determining the extracellular lactic dehydrogenase activity, the cellular viability and the biosynthetic production of collagen. In vitro permeation experiments through human stratum corneum and epidermis membranes were also carried out. Ultradeformable vesicles having sodium cholate molar fraction of 0.2 proved to be the most suitable topical carriers for asiaticoside. A sodium cholate content of >0.2 was observed to be cytotoxic probably due to its co-existence with other lipid aggregates, an example being mixed micelles. Asiaticoside-loaded ultradeformable vesicles with a sodium cholate molar fraction of 0.2 elicited the greatest degree of collagen biosynthesis in human fibroblasts. Ultradeformable vesicles provided the greatest in vitro skin permeation of asiaticoside showing a 10-fold increase with respect to the free drug solution and favoured an increase in in vivo collagen biosynthesis. Ultradeformable vesicles are therefore suitable carriers for the pharmaceutical and cosmetic application of the natural agent asiaticoside. [Copyright &y& Elsevier]

Abstract: The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed “Transfersomes” by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injection. Further research illustrated that the mechanisms of liposome action depended on the application regime and the vesicle composition and morphology. Ethical, health and supply problems with human skin have encouraged researchers to use skin models. Traditional models involved polymer membranes and animal tissue, but whilst of value for release studies, such models are not always good mimics for the complex human skin barrier, particularly with respect to the stratum corneal intercellular lipid domains. These lipids have a multiply bilayered organization, a composition and organization somewhat similar to liposomes. Consequently researchers have used vesicles as skin model membranes. Early work first employed phospholipid liposomes and tested their interactions with skin penetration enhancers, typically using thermal analysis and spectroscopic analyses. Another approach probed how incorporation of compounds into liposomes led to the loss of entrapped markers, analogous to “fluidization” of stratum corneum lipids on treatment with a penetration enhancer. Subsequently scientists employed liposomes formulated with skin lipids in these types of studies. Following a brief description of the nature of the skin barrier to transdermal drug delivery and the use of liposomes in drug delivery through skin, this article critically reviews the relevance of using different types of vesicles as a model for human skin in permeation enhancement studies, concentrating primarily on liposomes after briefly surveying older models. The validity of different types of liposome is considered and traditional skin models are compared to vesicular model membranes for their precision and accuracy as skin membrane mimics. [Copyright &y& Elsevier]

Colloids from an aqueous suspension can cross the skin barrier only through hydrophilic pathways. Various colloids have a different ability to do this by penetrating narrow pores of fixed size in the skin, or the relevant nano-pores in barriers modelling the skin. Such ability is governed by colloid adaptability, which must be high enough to allow penetrant deformation to the size of a pore in such barrier: for a 100 nm colloid trespassing the skin this means at least 5-fold deformation/elongation. (Lipid) Bilayer vesicles are normally more adaptable than the comparably large (lipid coated) fluid droplets. One of the reasons for this, and an essential condition for achieving a high bilayer adaptability and pore penetration, is a high bilayer membrane elasticity. The other reason is the relaxation of changing colloid''s volume-to-surface constraint during pore penetration; it stands to reason that such relaxation requires a concurrent, but only transient and local, bilayer permeabilisation. Both these phenomena are reflected in bilayer composition sensitivity, which implies non-linear pressure dependency of the apparent barrier penetrability, for example. Amphipats that acceptably weaken a membrane (surfactants, (co)solvents, such as certain alcohols, etc.) consequently facilitate controlled, local bilayer destabilisation and increase lipid bilayer flexibility. When used in the right quantity, such additives thus lower the energetic expense for elastic bilayer deformation, associated with pore penetration. Another prerequisite for aggregate transport through the skin is the colloid-induced opening of the originally very narrow (∼0.4 nm) gaps between cells in the barrier to pores with diameter above 30 nm. Colloids incapable of enforcing such widening—and simultaneously of self-adapting to the size of 20–30 nm without destruction—are confined to the skin surface. All relatively compact colloids seem to fall in this latter category. This includes mixed lipid micelles, solid (nano)particles, nano-droplets, biphasic vesicles, etc. Such colloids, therefore, merely enter the skin through the rare wide gaps between groups of skin cells near the organ surface. Transdermal drug delivery systems based on corresponding drug formulations, therefore, rely on simple drug diffusion through the skin; the colloid then, at best, can modulate drug transport through the barrier. In contrast, the adaptability-and stability-optimised mixed lipid vesicles (Transfersomes®, a trademark of IDEA AG) can trespass much narrower pathways between most cells in the skin; such highly adaptable colloids thus mediate drug transport through the skin. Sufficiently stable ultra-adaptable carriers, therefore, can ensure targeted drug delivery deep below the application site. This has already been shown in numerous preclinical tests and several phase I and phase II clinical studies. Drug delivery by means of highly adaptable drug carriers, moreover, allows highly efficient and well-tolerated drug targeting into the skin proper. Sustained drug release through the skin into systemic blood circulation is another field of ultradeformable drug carrier application. [Copyright &y& Elsevier]

Transferosomes containing an anti-fungal agent were prepared by Rotary Flask Evaporation -Sonication method. Eight batches were prepared in triplicate and vesicle size of each batch was determined. Plackett-Burman Design was employed to identify significant formulation and process parameters affecting vesicle size. The amount of lipid and surfactant, volume of ethanol and hydration medium as well as hydration time significantly affect the vesicle size.

• Nanoemulsions composed of N-oxide surfactants were prepared. • Morphology and physicochemical properties studied via SEM, TEM, DLS, MLS and EPR. • Formulations demonstrated promising skin drug delivery characteristics. • Curcumin loaded formulations demonstrated effectiveness in A.D.A.M. test. • N-oxide nanoemulsions could form topical delivery system for Candida skin infection. In this work we present comprehensive research on the formation, stability and structural properties of oil-in-water (o/w) nanoemulsions with the ability for topical administration, penetration of the skin and acting as antifungal agents against C. albicans. The studied nanoemulsions were composed of different ratios of double-head – single-tail surfactants {1-bis{[3-(N,N-dimethylamino)ethyl]amido}alkane-di-N-oxides (C n -MEDA), N,N-bis[3,3'-(dimethyl-amino)propyl]alkyl-amide di-N-oxides (C n (DAPANO) 2 } and single-head – single-tail surfactants {2-(alkanoylamino)-ethyldimethyl-amine-N-oxides (C n -EDA), and 3-(alkanoylamino) propyldimethylamine-N-oxides, (C n -PDA)} added to the oil {isooctane IO, isopropyl myristate IPM or glyceryl monocaprylate GM as (O)} and to the water phase (W). The phase behavior of the systems was examined by a titration method. Morphology of the resulting colloids was characterized by scanning and transmission electron microscopy, the particle size and size distributions determined by dynamic light scattering, and kinetic stability by multiple light scattering. While both surfactant types resulted in quite stable nanoemulsions, the systems formed using a single-headed one-tail surfactant were slightly more stable with GM or IPM. The microenvironmental properties of the nanoemulsions were studied by an electron paramagnetic resonance technique to distinguish the molecular dynamics of the different spin probes localized in the particular regions of the surfactant layers, depending on the surfactant structure and the system preparation. Skin permeation studies were performed to monitor transport through the skin, and changes in skin structure were followed using differential scanning calorimetry. Moreover, the activities of curcumin-loaded nanoemulsions stabilized by N-oxide surfactants against Candida albicans fungus were evaluated. To estimate in vitro efficacy, the suitability of an N-oxide nanoemulsion dressing against wound infection with biofilm C. albicans was assessed according to the Antibiofilm Dressing's Activity Measurement. We expect that the nanoemulsion formulations tested in this study will have potential for application as topical delivery systems for pharmaceutically active compounds in skin-related conditions. [ABSTRACT FROM AUTHOR]

Transferosomes, also known as transfersomes, are ultradeformable vesicles for transdermal applications consisting of a lipid bilayer with phospholipids and an edge activator and an ethanol/aqueous core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or amongst the lipid bilayer. Compared to liposomes, transferosomes are able to reach intact deeper regions of the skin after topical administration delivering higher concentrations of active substances making them a successful drug delivery carrier for transdermal applications. Most transferosomes contain phosphatidylcholine (C18) as it is the most abundant lipid component of the cell membrane, and hence, it is highly tolerated for the skin, decreasing the risk of undesirable effects, such as hypersensitive reactions. The most common edge activators are surfactants such as sodium deoxycholate, Tween® 80 and Span® 80. Their chain length is optimal for intercalation within the C18 phospholipid bilayer. A wide variety of drugs has been successfully encapsulated within transferosomes such as phytocompounds like sinomenine or apigenin for rheumatoid arthritis and leukaemia respectively, small hydrophobic drugs but also macromolecules like insulin. The main factors to develop optimal transferosomal formulations (with high drug loading and nanometric size) are the optimal ratio between the main components as well as the critical process parameters for their manufacture. Application of quality by design (QbD), specifically design of experiments (DoE), is crucial to understand the interplay among all these factors not only during the preparation at lab scale but also in the scale-up process. Clinical trials of a licensed topical ketoprofen transferosomal gel have shown promising results in the alleviation of symptons in orthreothritis with non-severe skin and subcutaneous tissue disorders. However, the product was withdrawn from the market which probably was related to the higher cost of the medicine linked to the expensive manufacturing process required in the production of transferosomes compared to other conventional gel formulations. This example brings out the need for a careful formulation design to exploit the best properties of this drug delivery system as well as the development of manufacturing processes easily scalable at industrial level. [ABSTRACT FROM AUTHOR]

Transferosomes containing an anti-fungal agent were prepared by Rotary Flask Evaporation -Sonication method. Eight batches were prepared in triplicate and vesicle size of each batch was determined. Plackett-Burman Design was employed to identify significant formulation and process parameters affecting vesicle size. The amount of lipid and surfactant, volume of ethanol and hydration medium as well as hydration time significantly affect the vesicle size. [ABSTRACT FROM AUTHOR]

Transferosomes containing an anti-fungal agent were prepared by Rotary Flask Evaporation -Sonication method. Eight batches were prepared in triplicate and vesicle size of each batch was determined. Plackett-Burman Design was employed to identify significant formulation and process parameters affecting vesicle size. The amount of lipid and surfactant, volume of ethanol and hydration medium as well as hydration time significantly affect the vesicle size.