Sorbitan ester organogels for transdermal delivery of sumatriptan

The partial phase behavior, rheological, and drug release characteristics of an organogel (OG) composed of water, isooctane and sorbitan esters, sorbitan monopalmitate (Span-40) and poly(oxyethylene)sorbitan monostearate (Polysorbate-60) were studied. Phase diagrams showed decreasing areas of optically isotropic organogel region depending on the surfactant ratio, K_w and drug incorporation. The nonbirefringent, clear isotropic solution suggested the reverse micellar/microemulsion nature of the organogel without any molecular ordering. The increase in drug concentration in OGs leads to increase in the viscosity and sol-gel transition temperature (T_g). Fractal dimension (d_f) values calculated for different compositions suggested that the density of the tubular network increases with increasing drug concentration in OGs. The release rate of the drug from OGs was found to be non-Fickian through the dialysis membrane. The permeation rate of sumatriptan from pig skin was 0.231 mg/h/cm² (781.9 nmol/h/cm²). The study indicates potential of OG as a reservoir system for transdermal drug delivery.     

Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats

A novel transdermal delivery of sumatriptan (ST) was attempted by application of dissolving microneedle (DM) technology. Dextran DM (d-DM) and hyaluronate DM (h-DM) were prepared by adding ST solution to dextran solution or hyaluronic acid solution. One DM chip, 1.0?×?1.0?cm, contains 100 microneedle arrays in a 10?×?10 matrix. The mean lengths of DMs were 496.6?±?2.9 μm for h-DM and 494.5?±?1.3 μm for d-DM. The diameters of the array basement were 295.9?±?3.9 μm (d-DM) and 291.7?±?3.0 μm (h-DM), where ST contents were 31.6?±?4.5?μg and 24.1?±?0.9?μg. These results suggest that ST was stable in h-DM. Each DM was administered to rat abdominal skin. The maximum plasma ST concentrations, C_max, and the areas under the plasma ST concentration versus time curves (AUC) were 44.6?±?4.9?ng/ml and 24.6?±?3.9?ng · h/ml for h-DM and 38.4?±?2.7?ng/ml and 14.1?±?1.5?ng · h/ml for d-DM. The bioavailabilities of ST from DMs were calculated as 100.7?±?18.8% for h-DM and 93.6?±?10.2% for d-DM. Good dose dependency was observed on C_max and AUC. The stability study of ST in DM was performed for 3 months under four different conditions, ?80, 4, 23, and 50°C. At the end of incubation period, they were, respectively, 100.0?±?0.3%, 97.8?±?0.2%, 98.8?±?0.2%, and 100.7?±?0.1%. These suggest the usefulness of DM as a noninvaisive transdermal delivery system of ST to migraine therapy.     

Insulin nanoparticles for transdermal delivery: preparation and physicochemical characterization and in vitro evaluation

Aim: This work is aimed to study the feasibility of insulin nanoparticles for transdermal drug delivery (TDD) using supercritical antisolvent (SAS) micronization process. Methods: The influences of various experimental factors on the mean particle size (MPS) of insulin nanoparticles were investigated. Moreover, the insulin nanoparticles obtained were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric (TG) analyses. Results: Under optimum conditions, uniform spherical insulin nanoparticles with a MPS of 68.2?±?10.8 nm were obtained. The Physicochemical characterization results showed that SAS process has not induced degradation of insulin. Evaluation in vitro showed that insulin nanoparticles were accorded with the Fick's first diffusion law and had a high permeation rate. Conclusion: These results suggest that insulin nanoparticles can have a great potential in TDD systems of diabetes chemotherapy.     

Physical characterization and cellular uptake of propylene glycol liposomes in vitro

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes–propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4?±?89.2?nm), high deformability (Elasticity index?=?48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents.     

Investigation of nanostructured lipid carriers for transdermal delivery of flurbiprofen

The aim of this study was to develop nanostructured lipid carriers (NLC) for transdermal delivery of Flurbiprofen (FP). The physical stability of FP-NLC and its in vitro permeation profile were investigated. After three months of storage at 4°C, 20°C, and 40°C, no significant differences between the evaluated parameters, such as pH value, the entrapment efficiency, particle size, and zeta potential were observed. In in vitro permeation studies, the cumulative permeated amounts and the release rate from FP-NLC were 412.53 ± 21.37 μg/cm² and 35.25 μg/cm²/h after 12 h (n = 6), respectively, while from saturated FP-PBS (pH = 7.4) were 90.83 ± 8.67 μg/cm² and 6.99 μg/cm²/h, respectively. These results indicated that the FP-NLC were with good physical stability and were able to improve the permeated amounts and the release rate of FP. It could potentially be exploited as a carrier with improved drug entrapment efficiency and permeated amount in the transdermal delivery of FP.     

Cholesterol derivative-based liposomes for gemcitabine delivery: preparation,in vitro,and in vivo characterization

As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol), was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112.57?±?1.25?nm, the encapsulation efficiency was above 99%, and the drug loading efficiency was about 50%. In vitro studies revealed that the Gem-Chol liposomes showed delayed drug release and long-term stability at 4?°C for up to 2 months. In vivo studies also showed the superiority of the Gem-Chol liposomes, and compared with free Gem, the Gem-Chol liposomes had longer circulation time. Moreover, an anti-tumor study in H₂₂ and S180 tumor models showed that liposomal entrapment of Gem-Chol improved the anti-tumor effect of Gem. This study reports a potential formulation of Gem for clinical application.     

Immobilization of aloin encapsulated into liposomes in Layer-by-layer films for transdermal drug delivery

Layer-by-layer (LbL) films have been exploited in drug delivery systems that may be used in the form of patches, but the encapsulation of poor water soluble drugs and their release with a controlled rate are still major challenges to be faced. In this paper, we demonstrate the controlled release of aloin (barbaloin), an important component of the widely used Aloe vera, encapsulated into liposomes and immobilized in LbL films with a polyelectrolyte. With a systematic study using fluorescence spectroscopy of aloin release from solutions and from LbL films with different phospholipid liposomes, we inferred that optimized release was achieved with aloin incorporated into palmitoyl oleyl phosphatidyl glycerol (POPG) or dipalmitoyl phosphatidyl glycerol (DPPG) liposomes immobilized in LbL films. Significantly, with this optimized system aloin was almost completely released within 30 h, with a small release rate at the end, which followed a sharp release in the first 5 h. Upon comparing the rates of the distinct systems, we conclude that the main factors controlling the release are the electrostatic interactions involving the negatively charged phospholipids. Because these interactions can be tuned in LbL films, the approach used here opens the way for new drug delivery systems to be developed with fine control of the drug release.     

Damar Batu as a novel matrix former for the transdermal drug delivery: in vitro evaluation

Purpose: Damar Batu (DB) is a novel film-forming biomaterial obtained from Shorea species, evaluated in this study for its potential application in transdermal drug delivery system. Methods: DB was characterized initially in terms of acid value, softening point, molecular weight (M_w), polydispersity index (M_w/M_n), and glass transition temperature (T_g). Neat, plasticized films of DB were investigated for mechanical properties. The biomaterial was further investigated as a matrix-forming agent for transdermal drug delivery system. Developed matrix-type transdermal patches were evaluated for thickness and weight uniformity, folding endurance, drug content, in vitro drug release study, and skin permeation study. Results: On the basis of in vitro drug release and in vitro skin permeation performance, formulation containing DB/Eudragit RL100 (60 : 40) was found to be better than other formulations and was selected as the optimized formulation. IR analysis of physical mixture of drug and polymer and thin layer chromatography study exhibited compatibility between drug and polymer. Conclusion: From the outcome of this study, it can be concluded that applying suitable adhesive layer and backing membrane-developed DB/ERL100, transdermal patches can be of potential therapeutic use.     

ATRP-based synthesis and characterization of light-responsive coatings for transdermal delivery systems

Abstract

The grafting of poly(hydroxyethylmethacrylate) on polymeric porous membranes via atom transfer radical polymerization (ATRP) and subsequent modification with a photo-responsive spiropyran derivative is described. This method leads to photo-responsive membranes with desirable properties such as light-controlled permeability changes, exceptional photo-stability and repeatability of the photo-responsive switching. Conventional track etched polyester membranes were first treated with plasma polymer coating introducing anchoring groups, which allowed the attachment of ATRP-initiator molecules on the membrane surface. Surface initiated ARGET–ATRP of hydroxyethylmethacrylate (where ARGET stands for activator regenerated by electron transfer) leads to a membrane covered with a polymer layer, whereas the controlled polymerization procedure allows good control over the thickness of the polymer layer in respect to the polymerization conditions. Therefore, the final permeability of the membranes could be tailored by choice of pore diameter of the initial membranes, applied monomer concentration or polymerization time. Moreover a remarkable switch in permeability (more than 1000%) upon irradiation with UV-light could be achieved. These properties enable possible applications in the field of transdermal drug delivery, filtration, or sensing.     

ATRP-based synthesis and characterization of light-responsive coatings for transdermal delivery systems

The grafting of poly(hydroxyethylmethacrylate) on polymeric porous membranes via atom transfer radical polymerization (ATRP) and subsequent modification with a photo-responsive spiropyran derivative is described. This method leads to photo-responsive membranes with desirable properties such as light-controlled permeability changes, exceptional photo-stability and repeatability of the photo-responsive switching. Conventional track etched polyester membranes were first treated with plasma polymer coating introducing anchoring groups, which allowed the attachment of ATRP-initiator molecules on the membrane surface. Surface initiated ARGET–ATRP of hydroxyethylmethacrylate (where ARGET stands for activator regenerated by electron transfer) leads to a membrane covered with a polymer layer, whereas the controlled polymerization procedure allows good control over the thickness of the polymer layer in respect to the polymerization conditions. Therefore, the final permeability of the membranes could be tailored by choice of pore diameter of the initial membranes, applied monomer concentration or polymerization time. Moreover a remarkable switch in permeability (more than 1000%) upon irradiation with UV-light could be achieved. These properties enable possible applications in the field of transdermal drug delivery, filtration, or sensing.     

Microemulsion for simultaneous transdermal delivery of benzocaine and indomethacin: in vitro and in vivo evaluation

This study investigated simultaneous transdermal delivery of indomethacin and benzocaine from microemulsion. Eucalyptus oil based microemulsion was used with Tween 80 and ethanol being employed as surfactant and cosurfactant, respectively. A microemulsion formulation comprising eucalyptus oil, polyoxyethylene sorbitan momooleate (Tween 80), ethanol and water (20:30:30:20) was selected. Indomethacin (1% w/w) and benzocaine (20% w/w) were incorporated separately or combined into this formulation before in vitro and in vivo evaluation. Application of indomethacin microemulsion enhanced the transdermal flux and reduced the lag time compared to saturated aqueous control. The same trend was evident for benzocaine microemulsion. Simultaneous application of the two drugs in microemulsion provided similar enhancement pattern. The in vivo evaluation employed the pinprick method and revealed rapid anesthesia after application of benzocaine microemulsion with the onset being 10?min and the action lasting for 50?min. For indomethacin microemulsion, the analgesic effect was recorded after 34.5?min and lasted for 70.5?min. Simultaneous application of benzocaine and indomethacin provided synergistic effect. The onset of action was achieved after 10?min and lasted for 95?min. The study highlighted the potential of microemulsion formulation in simultaneous transdermal delivery of two drugs.     

Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation

Vesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCT in vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm²/h as compared to 3.67 μg/cm²/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT.     

Preparation and characterization of PEG-modified polyurethane pressure-sensitive adhesives for transdermal drug delivery

Background: The purpose of this work was to develop novel pressure-sensitive adhesives (PSAs) for transdermal drug-delivery systems (TDDS) with proper adhesive properties, hydrophilicity, biocompatibility and high drug loading. Method: Polyethyleneglycol-modified polyurethane PSAs (PEG-PU-PSAs) were synthesized by prepolymerization method with PEG-modified co-polyether and hexamethylene diisocyanate. The effects of reaction temperature, catalyst, ratios of NCO/OH, co-polyether composition, and chain extender were investigated. Drug loading was studied by using thiamazole (hydrophilic drug), diclofenac sodium (slightly hydrophilic drug), and ibuprofen (lipophilic drug) as model drugs. In vitro drug-release kinetics obtained with Franz diffusion cell and dialysis membrane. Results: The results showed that when reaction temperature at 80°C, weight percentage of stannous octoate as catalyst at 0.05%, ratio of NCO/OH at 2.0–2.2, ratio of PEG/polypropylene glycol (PPG)/polytetramethylene ether glycol (PTMG) at 30/25–30/50–55, and weight percentage of glycol as chain extender at 4.5%, PEGPU-PSAs synthesized performed well on adhesive properties. Actually, PEG on the main chain of the PU could improve the hydrophilicity of PSAs, whereas PPG and PTMG could offer proper adhesive properties. Skin compatibility test on volunteers indicated that PEG-PU-PSAs would not cause any skin irritations. All the model drugs had excellent stabilizations in PEG-PU-PSAs. In vitro drug-release kinetics demonstrated that the drug release depended on drug-loading level and solubility of the drug. Conclusion: These experimental results indicated that PEG-PU-PSAs have good potential for applications in TDDS.     

Nanovesicular carrier-mediated transdermal delivery of tadalafil: i- formulation and physicsochemical characterization

The limited permeability of stratum corneum, the main skin barrier, towards pharmaceutical active ingredients represents the main obstacle encounter the transdermal drug delivery system. In the current study, penetration enhancer-containing nanoliposomes, that is, penetrosomes were formulated incorporating tadalafil to enhance its transdermal permeability. Hydration-sonication method was used to prepared penetrosomes bearing tadalafil. The prepared nanocarriers were characterized in terms of vesicles shape and surface morphology, size and size distribution, zeta potential, entrapment efficiency, and elasticity. Results pointed to that penetrosomes were spherical in shape with a unilamellar-closed structure in the nanometric narrow size range proved by their law span index. Penetrosomes formulations elaborated deformable vesicles more than the conventional liposomes, with the Penetrosomes-based Labrasol® being the most deformable formulation. Penetrosomes-ultraelastic nanoliposomes represent an attractive vehicle for transdermal delivery of tadalafil to treat erectile dysfunction.     

Ceramide-2 nanovesicles for effective transdermal delivery: development,characterization and pharmacokinetic evaluation

Context: The vesicles based on skin lipid have a drug localization effect and its main lipid, ceramide provides protective and regenerative effects while oleic acid (OA) is a penetration enhancer, however, it causes slight irritation, so we have formulated formulation incorporating both of these to develop a transdermal formulation for better permeation.

Objective: Present study investigated the preparation and characterization of physicochemical properties and permeation of nanovesicles of ceramide-2 containing OA and palmitic acid (PA) respectively and a commercial gel.

Materials and methods: The vesicles were made using ceramide 2, cholesterol (Chol), cholesteryl sulfate (CS) and OA or PA, respectively, using film hydration method. The vesicles were characterized for physicochemical properties, ex vivo permeation using human skin and pharmacokinetic parameters and anti-inflammatory activity in rats.

Results: The vesicles showed size at 102–125?nm while PDI was 0.11–0.13 and negative zeta potential. OV-3 showed highest entrapment efficiency. The drug fluxes were 92.02 and 8.920?μg/cm²/h, respectively, for OV-3 and PV-1. The C_max were 7.91 and 4.01?μg/ml at 4 and 6?h for OV-3 (2.5?mg) and PV-1 (10?mg), respectively. OV-3 and PV-1 showed 98.8% and 77.36% edema inhibition, respectively, at 3?h.

Discussion: Both formulations showed similar physical parameters and different permeation since OA get incorporated in vesicles and increases its permeability and ceramide makes sure that vesicles can rapidly traverse the stratum corneum.

Conclusion: OV-3 containing 3% OA showed optimum physical parameters and good permeation with maximum anti-inflammatory activity.     

Preparation, evaluation, and NMR characterization of vinpocetine microemulsion for transdermal delivery

A novel microemulsion was prepared to increase the solubility and the in vitro transdermal delivery of poorly water-soluble vinpocetine. The correlation between the transdermal permeation rate and structural characteristics of vinpocetine microemulsion was investigated by pulsed field gradient nuclear magnetic resonance (PFG-NMR). For the microemulsions, oleic acid was chosen as oil phase, PEG-8 glyceryl caprylate/caprate (Labrasol®) as surfactant (S), purified diethylene glycol monoethyl ether (Transcutol P®) as cosurfactant (CoS), and the double-distilled water as water phase. Pseudo-ternary phase diagrams were constructed to obtain the concentration range of each component for the microemulsion formation. The effects of various oils and different weight ratios of surfactant to cosurfactant (S/CoS) on the solubility and permeation rate of vinpocetine were investigated. Self-diffusion coefficients were determined by PFG-NMR in order to investigate the influence of microemulsion composition with the equal drug concentration on their transdermal delivery. Finally, the microemulsion containing 1% vinpocetine was optimized with 4% oleic acid, 20.5% Labrasol, 20.5% Transcutol P, and 55% double-distilled water (w/w), in which drug solubility was about 3160-fold higher compared to that in water and the apparent permeation rate across the excised rat skin was 36.4 ± 2.1 µg/cm²/h. The physicochemical properties of the optimized microemulsion were examined for the pH, viscosity, refractive index, conductivity, and particle size distribution. The microemulsion was stable after storing more than 12 months at 25°C. The irritation study showed that the optimized microemulsion was a nonirritant transdermal delivery system.     

Synthesis of piperazinylalkyl ester prodrugs of ketorolac and their in vitro evaluation for transdermal delivery

Ketorolac, an NSAID, has low intrinsic permeation capacity through the skin. In this work, seven piperazinylalkyl ester prodrugs of ketorolac were synthesized to enhance its skin permeation. The chemical hydrolysis and the stability in human serum at 37 degrees C were investigated in buffer solutions (pH 5.0 and 7.4) and in 80% human serum (pH 7.4), respectively. The prodrugs were chemically more stable at pH 5.0 than at pH 7.4 with prodrug 8 being the most stable (t(1/2) = 119.75 h and 11.97 h at pH 5 and 7.4, respectively). The prodrugs' t(1/2) in human serum ranged from 0.79 to 3.92 min. The prodrugs' aqueous solubility was measured in buffer solution at pH 5.0 and 7.4 and Log P(app) was measured by partitioning between buffer solution (pH 5.0 and 7.4) and n-octanol. The prodrugs were more lipophilic than ketorolac at pH 7.4. Skin permeation of ketorolac and prodrug 8, the most stable chemically, through rat skin was studied at pH 5.0 and 7.4. Prodrug 8 enhanced permeation by 1.56- and 11.39-fold at pH 5 and 7.4, respectively. This is attributed to higher lipophilicity at pH 7.4 and higher aqueous solubility at pH 5 compared to ketorolac.     

Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery

Objective: This study deals with the preparation and evaluation of a pluronic lecithin organogel (PLO gel) containing ricinoleic acid for the transdermal eyelid delivery of dexamethasone and tobramycin.

Methods: Five different PLO gel formulations (F1, F2, F3, F4 and F5) containing tobramycin (0.3%) and dexamethasone (0.1%) were prepared and compared to a conventional PLO gel (light mineral oil PLO gel, F6) with respect to physical appearance and viscosity. The optimized ricinoleic acid PLO gel formulation (F2) was further characterized for pH, gelation temperature, morphology and drug content. Ex vivo permeability of dexamethasone and bactericidal activity of tobramycin from formulation F2 was tested, and values were compared to the marketed Tobradex® eye ointment.

Results: No apparent changes in the physical appearance and consistency were observed when ricinoleic acid was used as the oil phase. The pH of the optimized ricinoleic acid PLO gel (formulation F2) was found to be 6.54 with a gelation temperature of 31?°C. The drug content of tobramycin and dexamethasone were found to be 102.8% and 100.14%, respectively. The penetration profile of dexamethasone from formulation F2 was found to be much higher than the marketed Tobradex® eye ointment. F2 showed a better antimicrobial activity and higher zones of inhibition when compared to the marketed Tobradex® eye ointment.

Conclusion: The findings of this investigation indicate that the ricinoleic acid PLO gel has the potential for use as a transdermal eyelid delivery system.     

Development of SLN and NLC enriched hydrogels for transdermal delivery of nitrendipine: in vitro and in vivo characteristics

The purpose of this research was to investigate novel particulate carrier systems such as solid lipid nanoparticles (SLN) and nanostructured lipid carrier (NLC) for transdermal delivery of nitrendipine (NDP). For this investigation, four different gel-forming agents were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles made from trimyristin (TM) were prepared by hot homogenization technique followed by sonication and then incorporated into the freshly prepared hydrogels. The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zetasizer, which shows that for all the tested formulations, more than 50% of the particles were below 250 nm after 90 days of storage at room temperature. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), which revealed fairly spherical shape of the formulations. The antihypertensive activity of the gels in comparison with that of oral NDP was studied using desoxy corticosterone acetate (DOCA)-induced hypertensive rats. It was observed that both carbopol SLN (A1) and carbopol NLC (B1) gels significantly controlled hypertension from the first hour (p < .05). The developed gels increased the efficacy of NDP for the therapy of hypertension. Both the SLN and NLC dispersions and the gels enriched with SLN and NLC possessed a sustained drug release over a period of 24 h, but the sustained effect was more pronounced with the SLN and the NLC gel formulations. Further, they were evaluated for zeta potential, entrapment efficiency, in vitro release, ex vivo permeation, and skin irritation studies.     

Transfersomes--a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation

This work describes the use of a novel vesicular drug carrier system called transfersomes, which is composed of phospholipid, surfactant, and water for enhanced transdermal delivery. The transfersomal system was much more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. In the present study transfersomes and liposomes were prepared by using dexamethasone as a model drug. The system was evaluated in vitro for vesicle shape and size, entrapment efficiency, degree of deformability, number of vesicles per cubic mm, and drug diffusion across the artificial membrane and rat skin. The effects of surfactant type, composition, charge, and concentration of surfactant were studied. The in vivo performance of selected formulation was evaluated by using a carrageenan-induced rat paw edema model. Fluorescence microscopy by using rhodamine-123 and 6-carboxyfluorescein as fluorescence probe was performed. The stability study was performed at 4°C and 37°C. An in vitro drug release study has shown a nearly zero order release of drug and no lag phase. The absence of lag phase in comparison to liposomes and ointment is attributed to the greater deformability, which may account for better skin permeability of transfersomes. In vivo studies of transfersomes showed better antiedema activity in comparison to liposomes and ointment, indicating better permeation through the penetration barrier of the skin. This was further confirmed through a fluorescence microscopy study. Finally, it may be concluded from the study that complex lipid molecules, transfersomes, can increase the transdermal flux, prolong the release, and improve the site specificity of bioactive molecules.