Formulation and optimization of a single-layer coat for targeting budesonide pellets to the descending Colon.

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon.

Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and eudragits L and s in the treatment of ulcerative colitis in rats.

The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60-70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4-0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon's tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.

The national health program for vitamin D supplementation in a developing country.

BACKGROUND: Previous studies have reported a high frequency of vitamin D deficiency (VDD) among different age groups in Iran. AIMS: In this study, the current coverage, status of vitamin D supplement taking, and program efficacy have been evaluated by the Office of Nutrition Department Society in Iran since 2014. METHODS: This study was conducted in collaboration with the International UNESCO center for Health-Related Basic Sciences and Human Nutrition and the Office of Nutrition Department Society. Sixty three medical universities were included in the current study to calculate the availability, accessibility and acceptability coverages. Furthermore, 3 medical universities including Mashhad (MUMS), Qom (QUMS) and Zahedan (ZAUMS) University of Medical Sciences were selected based on the results of the National Integrated Micronutrient Survey 2012 (NIMS-II study), in order to assess the status of vitamin D supplement intake in all age ranges. RESULTS: Quantitative analysis showed that availability coverage was 74.96% and 77.56% and accessibility was 80.70% and 83.26% in elderly and middle-aged subjects, respectively in 2018. The acceptability was approximately 43.7% and 43.9% among elderly and middle-aged participants, respectively. The availability and acceptability coverage was 80.99% and 85.0% among students in high schools. The mean vitamin D supplement uptake frequency was 27.0% (n = 387); 20.7% and 29.2% in rural and urban area, respectively (P = 0.001). The results showed that there was no significant difference in serum vitamin D levels between urban (20.41 ± 6.43 ng/ml) and rural areas, (P = 0.887). There was no significant difference in the serum vitamin D concentrations between men and women (P = 0.461). CONCLUSIONS: The frequency of taking vitamin D supplements was 27.0% in Iran in 2018. The frequency of taking of vitamin D supplements among vitamin D deficient group (serum vitamin D levels <19.99 ng/ml) was 43.6%. Lack of knowledge was the most important reason for not taking vitamin D supplement. Moreover, the serum vitamin D levels have increased in subjects aged 18-30 years old after the implementation of the vitamin D supplementary program.

A review on curcumin colon-targeted oral drug delivery systems for the treatment of inflammatory bowel disease.

Synthetic drugs and monoclonal antibodies are the typical treatments to combat inflammatory bowel disease (IBD). However, side effects are present when these treatments are used, and their continued application could be restricted by the high relapse rate of the disease. One potential alternative to these treatments is the use of plant-derived products. The use curcumin is one such treatment option that has seen an increase in usage in treating IBD. Curcumin is derived from a rhizome of turmeric (Curcuma longa), and the results of studies on the use of curcumin to treat IBD are promising. These studies suggest that curcumin interacts with cellular targets such as NF-κB, JAKs/STATs, MAPKs, TNF-α, IL-6, PPAR, and TRPV1 and may reduce the progression of IBD. Potentially, curcumin can be used as a therapeutic agent for patients with IBD when it reduces the incidence of clinical relapse. This review discusses the strategies utilized in designing and developing an oral colonic delivery dosage form of curcumin.

Recent progress in the graphene-based biosensing approaches for the detection of Alzheimer's biomarkers.

Alzheimer's disease (AD) is one of the most common types of neurodegenerative disorders. It is possible to identify AD early thanks to the measurement of specific biomarker levels. Owing to crucial roles of biomarkers in the AD, the detection of AD-related biomarkers may be suitable for predictive identification of AD. Biosensors is a novel tool that could be beneficial to appreciate recognition of several AD biomarkers as early as possible. Graphene and its derivatives containing graphene oxide (GO) and reduced-GO (rGO) can be good choice for biosensing approaches due to their unique properties. GO/rGO-based biosensors or nanosensors have been widely used for the determination of AD biomarkers. In this article, the general aspects of AD, its biomarkers, biosensors, and GO are overviewed. In addition, this review provides the current developments in the applications of graphene-based biosensors for recognition of AD biomarkers. Future perspectives and challenges of graphene-based biosensing as a new approach for detection of AD are discussed in brief as well.

Preparation of stable enteric folic acid-loaded microfiber using the electrospinning method.

Objectives: Folic acid is an essential vitamin, labile to hydrolysis in the acidic environment of the stomach with low water solubility and bioavailability. In order to solve these problems, enteric oral folic acid-loaded microfibers with a pH-sensitive polymer by electrospinning method were prepared. Materials and Methods: Electrospinning was performed at different folic acid ratios and voltages. Fibers were evaluated in terms of mechanical strength, acidic resistance, and drug release. Additionally, DSC (Differential Scanning Calorimetry), FTIR (Fourier-transform infrared spectroscopy), and XRD (X-ray diffraction) analyses were performed on the optimal formulation. Results: Drug ratio and voltage had a considerable effect on fibers' entrapment efficiency, acid resistance, and mechanical strength. Based on the obtained results, the optimum formulation containing 1.25% of the drug/polymer was prepared at 18 kV. The entrapment efficiency of the optimal sample was above 90% with an acid resistance of higher than 70%. The tensile test confirmed the high mechanical properties of the optimum microfiber. DSC and XRD tests indicated that folic acid was converted to an amorphous form in the fiber structure and the FTIR test confirmed the formation of a chemical bond between the drug and the polymer. The release of the drug from the optimal fiber was about 90% in 60 min. Conclusion: In conclusion, the optimal formulation of folic acid with proper mechanical properties can be used as a candidate dosage form for further bioavailability investigations.

Optimization study of combined enteric and time-dependent polymethacrylates as a coating for colon targeted delivery of 5-ASA pellets in rats with ulcerative colitis.

Formulation design for colon-specific delivery of 5-aminosalicylic acid (5-ASA) could bring some therapeutic benefits in the treatment of ulcerative colitis (UC). In the current study, a 32 full factorial design was used to predict optimum coating composed of two enteric (poly methacrylic acid, methyl methacrylates 1:2 and 1:1) and time-dependent (poly ethyl acrylate, methyl methacrylate, trimethylammonio ethyl methacrylate chloride 1:2:0.1) polymethacrylates for colon-specific delivery of 5-ASA pellets. A unique coating composition and coating level predicted by the model was applied onto either inulin-free 5-ASA pellets or inulin-bearing 5-ASA pellets and the coated pellets were examined by dissolution test in-vitro. The coated pellets were also tested in a rat model of UC and compared with the a commercially available colonic delivery system of 5-ASA. The ratio of the two enteric polymethacrylates and time-dependet polymethacrylate of 16:64:20 w/w at a coating level of 15% was discovered as the optimum coating for delivery of 5-ASA pellets to the colon. In general, the coated pellets offered a better therapeutic outcome compared to commercially available colonic delivery system of 5-ASA and uncoated pellets in terms of colitis activity index and the colon's tissue enzymes of MDA and GSH. It seems that the coating composed of enteric and pH-dependent polymethacrylates could tune up the rate of drug release from 5-ASA-coated pellets and trigger drug release based on pH and time.

Preparation and Characterization of a Novel Multiparticulate Dosage Form Carrying Budesonide-Loaded Chitosan Nanoparticles to Enhance the Efficiency of Pellets in the Colon.

An attempt was made to conquer the limitation of orally administered nanoparticles for the delivery of budesonide to the colon. The ionic gelation technique was used to load budesonide on chitosan nanoparticles. The nanoparticles were investigated in terms of size, zeta potential, encapsulation efficiency, shape and drug release. Then, nanoparticles were pelletized using the extrusion-spheronization method and were investigated for their size, mechanical properties, and drug release. Pellets were subsequently coated with a polymeric solution composed of two enteric (eudragit L and S) and time-dependent polymers (eudragit RS) for colon-specific delivery. All formulations were examined for their anti-inflammatory effect in rats with induced colitis and the relapse of the colitis after discontinuation of treatment was also followed. The size of nanoparticles ranged between 288 ± 7.5 and 566 ± 7.7 nm and zeta potential verified their positive charged surface. The drug release from nanoparticles showed an initial burst release followed by a continuous release. Pelletized nanoparticles showed proper mechanical properties and faster drug release in acidic pH compared with alkaline pH. It was interesting to note that pelletized budesonide nanoparticles released the drug throughout the GIT in a sustained fashion, and had long-lasting anti-inflammatory effects while rapid relapse was observed for those treated with conventional budesonide pellets. It seems that there is a synergistic effect of nanoformulation of budesonide and the encapsulation of pelletized nanoparticles in a proper coating system for colon delivery that could result in a significant and long-lasting anti-inflammatory effect.

The Effect of Thermal-Treating on Drug Release from Sustained Release Alginate-Eudragit RS Matrices.

Purpose: The main objective of the present study was to develop the colonic delivery system for 5-aminosalicylic acid (5-ASA) as an anti-inflammatory drug. Methods: Matrix pellets containing various proportions of alginate, calcium and Eudragit® RS were prepared by extrusion-spheronization technique. Thermal treatment was used to investigate the effect of the curing process on the surface morphology, mechanical and physicochemical properties and in vitro drug release profile of pellets. Based on the obtained results optimal formulations were selected to coating by the Eudragit® RS and subjected to a subsequent continuous dissolution test. Results: Image analysis and also scanning electron microscopy results proved acceptable morphology of the pellets. The fourier transform infrared spectroscopy and differential scanning calorimetry studies ruled out any interactions between the formulation's components. Curing process did not alter the mechanical properties of pellets. The release rate of the drug from matrices was prolonged due to the decreased porosity of cured pellets. Furthermore, selected cured pellets which coated with Eudragit® RS, prevented undesired premature drug release. Conclusion: Formulation containing 17.5% calcium, 17.5% alginate, and a coating level of 10% demonstrated enhanced drug release so that provided resistance to acidic conditions, allowing complete drug release in alkaline pH, mimicking colonic environment. The slow and consistent drug release from this formulation could be used for treatment of a broader range of Inflammatory bowel disease (IBD) patients especially in whom colonic pH levels have been measured at lower than pH 7.0.

Application of inulin/Eudragit RS in 5-ASA pellet coating with tuned, sustained-release feature in an animal model of ulcerative colitis.

A tunable release of 5-aminosalicylic acid (5-ASA) could bring therapeutic benefits in the treatment of inflammatory bowel disease (IBD). A 32 factorial design was used to achieve a tuned delivery of 5-ASA pellets in the small and large intestine using a coating composed of inulin/Eudragit RS (RS). The ratio of inulin/RS and coating level were independent variables while the dependent variables were the percent of drug release at pH 1.2 in 2 h and total release of drug in 10 h at pH 6.8. 5-ASA release from pellets was examined at different pH levels and the therapeutic efficacy of the optimum pellets was compared to 5-ASA pellets of Pentasa in rats with ulcerative colitis. The inulin/RS of 18/82 at a coating level of 16% was found to be the optimum for delivery of the drug to the small and large intestine. The coated pellets offered a superior therapeutic outcome compared to uncoated pellets and Pentasa in terms of colitis activity index (CAI), and the colon's tissue enzymes of GSH and MDA. The optimum coating composed of inulin and RS could offer a tuned sustained release of 5-ASA throughout the small and large intestine with the sensitivity of drug release to microbial degradation.

Design and physico-mechanical evaluation of fast-dissolving valsartan polymeric drug delivery system by electrospinning method.

Objectives: Chronic hypertension is a pervasive morbidity and the leading risk factor for cardiovascular diseases. Valsartan, as an antihypertensive drug, has low solubility and bioavailability. The application of orodispersible films of valsartan is suggested to improve its bioavailability. With this dosage form, the drug dissolves rapidly in saliva and is absorbed readily without the need for water. Materials and Methods: For this purpose, valsartan with polyvinylpyrrolidone (PVPK90) polymer were exposed to the electrospinning technique to construct orodispersible nanofilms. The optimum obtained nanofiber, selected by Design-Expert software, was evaluated in terms of mechanical strength for evaluation of the flexibility and fragility of the nanofibers. The drug content, wettability, and disintegration tests, as well as the release assessment of the nanofibers, were performed followed by DSC, FTIR, and XRD assays. Results: The uniform nanofibers' diameter increased with the increase of the polymer concentration. The tensile test verified a stress reduction at the yield point as the polymer concentration increased. Then, the 492 nm nanofiber with above 90% drug encapsulation, containing 8% polymer and 18% valsartan made below 9 kV, was selected. The wetting time was less than 30 sec and over 90% of the drug was released in less than 2 min. The XRD and DSC studies also confirmed higher valsartan solubility due to the construction alternations in nanofibers. The FTIR examination indicated the chemical bonding between the drug and the polymer. Conclusion: The selected nanofibers of valsartan present the essential drug feature and acceptable drug release for further investigations.

Synthesis of a novel PEGylated colon-specific azo-based 4- aminosalicylic acid prodrug.

OBJECTIVES: 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue. MATERIALS AND METHODS: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content. RESULTS: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr. CONCLUSION: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.

Screening of different polysaccharides in a composite film based on Eudragit RS for subsequent use as a coating for delivery of 5-ASA to colon.

This study aims at identifying the more suitable polysaccharide in a composite film based on Eudragit RS for 5-ASA delivery to the colon. Different polysaccharides (pectin, chitosan, guar, inulin, and dextran) were examined. The mechanical properties, swelling index, loss of film mass and permeability of films to 5-ASA were recorded at simulating gastric (SGF), intestinal (SIF) and colonic fluids (SCF). Films containing inulin or dextran were more flexible and showed better mechanical properties. Films containing chitosan, pectin or guar exhibited extensive swelling in SGF and SIF. Loss of film mass and drug permeation was more pronounced in SCF than SIF for all samples indicating their sensitivity to colonic bacteria. However, films containing inulin or dextran showed minimum swelling index in SGF and SIF and the highest ratio of permeability in SCF to SIF. Accordingly, inulin and dextran are suggested as appropriate polysaccharides in a film based on Eudragit RS for colon delivery of 5-ASA.

A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems.

Site-specific colon drug delivery is a practical approach for the treatment of local diseases of the colon with several advantages such as rapid onset of action and reduction of the dosage of the drug as well as minimization of harmful side effects. 5-aminosalicylic acid (5-ASA) is a drug of choice in the treatment of inflammatory bowel disease and colitis. For the efficient delivery of this drug, it is vital to prevent 5-ASA release in the upper part of the gastrointestinal tract and to promote its release in the proximal colon. Different approaches including chemical manipulation of drug molecule for production of prodrugs or modification of drug delivery systems using pH-dependent, time-dependent and/or bacterially biodegradable materials have been tried to optimize 5-ASA delivery to the colon. In the current review, the different strategies utilized in the design and development of an oral colonic delivery dosage form of 5-ASA are presented and discussed.

Investigation of using pectin and chitosan as natural excipients in pellet formulation.

This study aimed to evaluate the potential of applying pectin and chitosan polysaccharides in pellet formulation. These biopolymers have advantages such as biocompatibility, low toxicity, low price and easy processing which make them interesting candidates for drug delivery purposes. Careful control of pellet porosity is essential to achieve an appropriate drug release profile. Replacing microcrystalline cellulose (MCC) with polysaccharides, especially pectin, leads to increased pellet porosity. Theophylline, dimenhydrinate and ibuprofen were chosen as model drugs. Investigation of possible ionic interactions between drugs and excipients is crucial to optimize the formulation of pellets with acceptable drug release. Differential scanning calorimetry of chitosan showed an endothermic peak; however, this peak was not observed in thermograms of the pectin, implying the lack of interaction between polysaccharides. Fourier transform infrared analysis did not indicate any interaction between drugs and polymers. Incorporation of MCC into the pellet formulation significantly increased the mean dissolution time while substitution of MCC with polysaccharides led to a faster release for each of the three drugs - that were different in their net charges - in both acidic and buffer media. These results highlight the potential value of polysaccharides in improving drug delivery characteristics of pharmaceutical pellets.

Evaluation of ethylcellulose and its pseudolatex (Surelease) in preparation of matrix pellets of theophylline using extrusion-spheronization.

OBJECTIVES: This study evaluates the effect of substitution of microcrystalline cellulose (MCC) with ethylcellulose (EC) on mechanical and release characteristics of theophylline pellets. MATERIALS AND METHODS: The effect of addition of EC was investigated on characteristics of pellets with varying drug content prepared by extrusion-spheronization. Also the effect of type of granulating liquid (water or Surelease) was investigated on characteristics of selected pellets. The pellets were characterized for particle size (sieve analysis), mechanical strength, morphology (microscopy), thermal (DSC) and dissolution behaviors. RESULTS: The exrtudability of the wet mass was reduced upon inclusion of EC so that complete replacement of MCC was not possible. Increase in EC percentage led to lower production yield and formation of pellets with larger diameter and slightly rough surfaces. Inclusion of EC also affected the mechanical properties of pellets but had negligible effect on drug release profile. The surface of selected pellets became smoother and their production yield increased upon the use of Surelease as granulating liquid. In addition the rate of drug release decreased to some extent when Surelease was used. CONCLUSION: Preparation of theophylline pellets with EC alone was not possible in process of extrusion-spheronization. Partial replacement of MCC with EC changed physicomechanical properties of pellets but hardly affected drug release. Although the use of Surelease as granulation liquid slightly decreased the rate of drug release, desirable matrix pellets with sustained drug release could not be produced. Despite this outcome however, these pellets could benefit from reduced coating thickness for drug release control.

Indomethacin electrospun nanofibers for colonic drug delivery: In vitro dissolution studies.

Generally, although the conventional drug delivery systems, such as using only pH-dependent polymers or time-dependent release systems are popular, the individuals' variations of physiological conditions usually lead to premature or imperfect drug release from each of these systems. Therefore, a combination of pH- and time-dependent polymers could be more reliable for delivering drugs to the lower GI tract such as colon. To this end, electrospinning method was used as a fabrication approach for preparing electrospun nanofibers of indomethacin aimed for colon delivery. Formulations were prepared based on a 32 full factorial design. Independent variables were the drug:polymer ratio (with the levels of 3:5, 4.5:5 and 6:5w/w) and Eudragit S:Eudragit RS w/w ratio (20:80, 60:40 and 100:0). The evaluated responses were drug release at pH 1.2, 6.4, 6.8 and 7.4. Combinations of Eudragit S (ES), Eudragit RS (ERS) and drug based on factorial design were loaded in 10ml syringes. Electrospinning method was used to prepare electrospun nanofibers from electrospinning solutions. Conductivity and the viscosity of the solutions were analyzed prior to electrospinning. After collection, the nanofibers were evaluated in terms of morphology and drug release. It was shown that the ratio of drug:polymer and polymer:polymer were pivotal factors to control the drug release from nanofibers. A formulation containing Eudragit S:Eudragit RS (60:40) and drug:polymer ratio of 3:5 exhibited the most appropriate drug release as a colon delivery system with a minor release at pH 1.2, 6.4 and 6.8 and major release at pH 7.4. Nanofibers resulted from this formulation were also more uniform and contained fewer amounts of beads. It was demonstrated that the electrospinning could be regarded as a modern approach for the preparation of colon drug delivery systems leading to marketable products.

Prediction of Optimum Combination of Eudragit RS/Eudragit RL/Ethyl Cellulose Polymeric Free Films Based on Experimental Design for Using as a Coating System for Sustained Release Theophylline Pellets.

PURPOSE: The physicochemical properties of free films made from different mixtures of sustained release polymers were investigated, and an optimum formulation coating on drug containing pellets, based on the study of free film was evaluated. METHODS: In order to determine the effect of different variables on the permeability and swelling of films and procedure optimization, the experimental design was fulfilled based on the statistical method of a 3(3) full factorial design, and according to this method 27 formulations were prepared. The films were prepared using casting-solvent evaporation method. Water vapor permeability, the swelling and permeability of free films in both acidic and buffer media, were carried out. Then, the pellets containing theophylline were coated with the optimum formulation. RESULTS: The results of this study demonstrated that an increase in the free film thickness and Eurdragit RS ratio in films lowered the water vapor transmission (WVT), the swelling and the permeability of all formulations, while an increase in the quantity of ethylcellulose, up to a specific ratio (approximately 40%), decreased the permeability and swelling. The most optimum free film formulation was made up of 60% Eudragit RS and 40% ethylcellulose. CONCLUSION: Pellets coated with a 10% coating level of ethylcellulose and Eudragit RS (4:6) showed suitable release properties and could serve as a favorable sustained release system for theophylline.

Statistical optimization of tretinoin-loaded penetration-enhancer vesicles (PEV) for topical delivery.

BACKGROUND: The aim of this study was to develop and optimize deformable liposome for topical delivery of tretinoin. METHODS: Liposomal formulations were designed based on the full factorial design and prepared by fusion method. The influence of different ratio of soy phosphatidylcholine and transcutol (independent variables) on incorporation efficiency and drug release in 15 min and 24 h (responses) from liposomal formulations was evaluated. Liposomes were characterized for their vesicle size and Differential Scanning Calorimetry (DSC) was used to investigate changes in their thermal behavior. The penetration and retention of drug was determined using mouse skin. Also skin histology study was performed. RESULTS: Particle size of all formulations was smaller than 20 nm. Incorporation efficiency of liposomes was 79-93 %. Formulation F7 (25:5) showed maximum drug release. Optimum formulations were selected based on the contour plots resulted by statistical equations of drug release in 15 min and 24 h. Solubility properties of transcutol led to higher skin penetration for optimum formulations compared to tretinoin cream. There was no significant difference between the amount of drug retained in the skin by applying optimum formulations and cream. Histopatological investigation suggested optimum formulations could decrease the adverse effect of tretinoin in liposome compared to conventional cream. CONCLUSION: According to the results of the study, it is concluded that deformable liposome containing transcutol may be successfully used for dermal delivery of tretinoin.