Development and evaluation of topical films containing phytoestrogenic diaryheptanoids from Curcuma comosa extract

Rational: Phytoestrogens have been found to delay signs of skin aging in post-menopausal women, in a way similar to the effects of estrogens. Diarylheptanoids from a rhizome of traditional Thai herb named Curcuma comosa is considered to be a novel class of phytoestrogens.

Objectives: The aims of this study were to prepare effective topical films using mixed types and vary ratios of hydrophobic (Eudragit RL, Eudragit RS, and Eudragit NE) and hydrophilic polymer (hydroxylpropyl methycellulose, HPMC) with Transcutol as a permeation enhancer for delivery of diarylheptanoids to improve signs of skin aging in post-menopausal women.

Material and methods: Topical films were characterized for their physical and mechanical properties. In vitro release, skin permeation and accumulation were evaluated using Franz diffusion cell and the concentrations of diarylheptanoids were determined using high-performance liquid chromatography.

Results: The combined formulations between HPMC and Eudragit NE showed the satisfactory physical and mechanical properties, and also provided the highest amount of drug released compared to Eudragit RL and Eudragit RS. When the proportion of HPMC amount in the polymer matrix increased, the cumulative drug release also increased (HPMC: Eudragit NE 6:4?>?5:5?>?4:6). Moreover, they provided a high accumulation of diarylheptanoids within skin when using transcutol as a permeation enhancer.

Conclusion: The obtained data provided the skin permeation and accumulation behavior of diarylheptanoids, indicating the feasibility of a skin delivery of the C. comosa extract. The developed films might be topically used as an alternative therapy for protection of skin aging in peri and post-menopausal women.     

Analysis of hair follicle penetration of lidocaine and fluorescein isothiocyanate-dextran 4 kDa using hair follicle-plugging method

Objective: Skin appendages including hair follicles (hfs) and the stratum corneum (sc) are beginning to be recognized as important permeation pathways for the skin permeation of drugs, but their detailed role is not yet clear. To investigate the contribution of hfs to drug permeation, we conducted skin permeation tests by controlling the hf contribution with a hf-plugging method.

Method: Lidocaine (LC) and fluorescein isothiocyanate-dextran 4?kDa (FD-4) were selected as model drugs and pig ear skin was used as model skin.

Results: Skin permeabilities of ionized LC and FD-4 decreased with hf-plugging, whereas no change was observed for the skin permeation of unionized LC. A fairly good correlation was found for ionized LC and FD-4 between skin permeability and the number of hfs plugged. Permeation parameters of model drugs for both skin pathways were calculated utilizing Fick's second law of diffusion. Consequently, the sc pathway could highly contribute to the permeation of unionized LC, since unionized LC shows markedly high partition to the sc. In contrast, the hf pathway could contribute to the permeation of ionized LC and FD-4, since these had high distributions to the hf pathway in spite of its very small surface area relative to whole skin surface area.

Conclusion: The hf pathway must be important for the skin permeation of ionized compounds and hydrophilic high molecular compounds. hf-plugging is also a useful method for assessing the skin permeability of compounds through the hf pathway.     

In vitro and in vivo evaluation of a desonide gel-cream photostabilized with benzophenone-3

Context: Our group previously reported the photoinstability of some desonide topical commercial formulations under direct exposure to UVA radiation.

Objective: This study aimed to prepare and characterize a gel-cream containing desonide, with greater photostability than the commercial gel-cream (C-GC). Benzophenone-3 (BP-3) was used as a photostabilizing agent.

Methods: The gel-cream developed (D-GC) containing BP-3 at 0.1% was prepared and characterized regarding its pH, drug content, spreadability, viscosity, in vitro drug release and in vitro permeation. The in vivo anti-inflammatory effect was assessed by ear edema measurement, croton oil-induced acute skin inflammation and myeloperoxidase assay.

Results and Discussion: D-GC presented characteristics compatible with topical application, appropriate drug content and good spreadability, and non-Newtonian behavior with pseudoplastic flow. D-GC showed a good photostability profile, presenting a desonide content of 95.70% after 48?h of exposure to UVA radiation, and stability under room conditions during 60 days. The amount of desonide released from D-GC and C-GC was 57.8 and 51.7?µg/cm², respectively, measured using the vertical Franz cell. The in vitro skin permeation showed that desonide reached the site of action of the topical corticosteroids, from both formulations; however, the desonide amount retained in the dermis was lower with D-GC. The in vivo evaluation of topical anti-inflammatory activity indicated that D-GC presented the same biological effect as C-GC.

Conclusion: D-GC represents a promising approach to treat dermatological disorders, since it presented satisfactory physicochemical characteristics, the same biological activity as C-GC and superior photostability, conferred by the addition of BP-3 at 0.1%.     

Permeation Studies Comparing Cobra Skin with Human Skin Using Nicotine Transdermal Patches

Cobra skin (Naja Naja Khaotia) was used as a barrier for an in vitro permeation study using nicotine. Fluxes of nicotine that permeated from Nicotinell ® through cobra skin (CS) taken from the head, body, and tail were 233.93 ± 16.08, 206.87 ± 19.00, and 211.26 ± 22.93 μg/cm²/hr^1/2, respectively (n=6). This indicated no significant difference (p >. 05). Abdominal human epidermis (HE), obtained from cadavers, and the CS provided identical permeation kinetics for nicotine, which can be described by M_t = 4M_α=(Dt π L²)^1/2. The mean flux of nicotine formulated as an acrylic transdermal patch that permeated through HE was 137.92 ± 67.79 μg/cm²/hr^1/2 (4 specimens, n= 12), whereas that through CS was 180.13 ± 41.05 μg/cm²/hr^1/2 (4 specimens, n= 15). The ratio of the fluxes of nicotine from formulated patches having three different nicotine contents using CS and HE was 1.22 to 1, respectively, for each of the patches irrespective of nicotine content. The coefficients of variation of the nicotine permeated were 22.79% and 49.15% for CS and HE, respectively, that is, a narrower variation of results was obtained with CS. This indicated that CS could be used for nicotine permeation studies.     

Enhanced oral bioavailability of Wurenchun (Fructus Schisandrae Chinensis Extracts) by self-emulsifying drug delivery systems

Background: White petrolatum is broadly used as an ointment vehicle, although hydrophilic drugs cannot be easily dissolved in the vehicle. Method: The aim of this study was to evaluate the release and skin permeation profiles of a model hydrophilic agent, N1-[2-(4-guanidinophenyl)-1(S)-(N-methylcarbamoyl)ethyl]-N4-hydroxy-2(R)-iso-butyl-3(S)-(3-phenylpropyl)succinamide hydrochloride (FYK-1388b), from the ointment. Results: The release rate of FYK-1388b was very low; however, high skin permeation and skin content of the drug were found. We supposed that this was due to endogenous lipids or sebum, because white petrolatum had a high affinity to these lipids. To evaluate the effect of lipids on the enhanced release and skin permeation of FYK-1388b, ‘preapplied white petrolatum’ was made by applying the drug-free white petrolatum on the hairless rat skin for 6 hours. Then the drug ointment was prepared using the ‘preapplied white petrolatum’. The release rate of FYK-1388b was markedly increased from the ‘preapplied ointment’ compared with the ‘original ointment’. In addition, much higher skin permeation was also obtained using the ‘preapplied ointment’. Separately, cholesteryl oleate, cholesterol, and ceramides were found in the ‘preapplied white petrolatum’. Conclusion: Thus, these endogenous lipids on the skin surface may enhance the release and skin permeation of FYK-1388b from white petrolatum ointment.     

Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery

Objective: The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system.

Materials and methods: With bovine albumin-fluorescein isothiocyanate conjugate (FITC-BSA) as a vaccine model, formulations were selected with the construction of pseudo-ternary phase diagrams and a short-term stability study. The size of the emulsion droplets was furthered optimized with high-pressure homogenization. The optimized formulation was evaluated for its skin permeation efficiency. In vitro skin permeation studies were conducted with shaved BALB/c mice skin samples with a Franz diffusion cell system. Different drug concentrations were compared, and the effect of the nanoemulsion excipients on the permeation of the FITC-BSA was also studied.

Results: The optimum homogenization regime was determined to be five passes at 20?000?psi, with no evidence of protein degradation during processing. With these conditions, the particle diameter was 85.2?nm?±?15.5?nm with a polydispersity index of 0.186?±?0.026 and viscosity of 14.6 cP?±?1.2 cP. The optimized formulation proved stable for 1 year at 4?°C. In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC-BSA through skin with an enhancement ratio of 4.2 compared to a neat control solution. Finally, a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23.44?μg/cm²/h for the nanoemulsion as opposed to 6.10?μg/cm²/h for the emulsifiers.

Conclusion: A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured. The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle.     

Chitosan–glycolic acid: a possible matrix for progesterone delivery into skin

Background: Chitosan-EDTA is an interesting matrix for dermal delivery; however, the adhesiveness is too small. Therefore, the purpose of this study was to investigate chitosan-glycolic acid as possible dermal matrix for progesterone in comparison to chitosan-EDTA and carrageenan. Method: After preparation of the chitosan-glycolic acid salt and characterization by NMR and FTIR, tensile studies using porcine skin and rheology measurements as well as standard diffusion experiments using dermatomed porcine skin were performed. Results: Results showed an improved skin adhesiveness of chitosan-glycolic acid and increased viscosity. Skin diffusion studies indicated the highest cumulative permeation of progesterone after 48 hours from chitosan-glycolic acid followed by carrageenan and chitosan-EDTA. A possible explanation might be a longer residence time on skin caused by the higher adhesiveness and with it higher progesterone skin permeation. Conclusion: Chitosan-glycolic acid can be recommended as a suitable polymer for hydrogels and an adhesive matrix for a transdermal application of progesterone exhibiting excellent skin adhesiveness and permeation properties.     

Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in efficient treatment of cellulite

Context: Cellulite refers to dimpled appearance of the skin, usually located in the thighs and buttocks regions of most adult women.

Objective: The aim of this study was to formulate topically used caffeine-loaded solid lipid nanoparticle (SLN) for the treatment of cellulite.

Methods: SLNs were prepared by hot homogenization technique using Precirol® as lipid phase. The physical characterization and stability studies of SLNs as well as in vitro skin permeation and histological studies in rat skin were conducted.

Results: The mean particle size, encapsulation efficiency and loading efficiency percentages for optimized SLN formulation were 94?nm, 86 and 28%, respectively. In vitro drug release demonstrated that caffeine-loaded SLN incorporated into carbopol made hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to the caffeine hydrogel over 24?h. Caffeine-loaded SLNs showed a good stability during 12 months of storage at room temperature. The DSC and XRD results showed that caffeine was dispersed in SLN in an amorphous state. In vitro permeation studies illustrated higher drug accumulation in the skin with caffeine-SLN-hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel, representing lower systemic absorption. In contrast with caffeine hydrogel, the histological studies showed the complete lysis of adipocytes by administration of caffeine-SLN-hydrogel in the deeper skin layers.

Conclusion: Results of this study indicated that SLNs are promising carrier for improvement of caffeine efficiency in the treatment of cellulite following topical application on the skin.     

Formulation study of a patch containing propranolol by design of experiments

Objective: To evaluate the feasibility of a transdermal patch containing propranolol (PR).

Method: Skin penetration enhancers (SPEs) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2⁴ full factorial design. The permeation profile of PR from the formulations was assessed in in vitro permeation studies performed by using Franz diffusion cells and human epidermis as membrane. Finally, skin irritation was evaluated by the Draize test.

Results: N-methyl pyrrolidone (NMP) resulted as the best SPE: in addition, the critical factors influencing the PR diffusion through the human epidermis when loaded in the patch resulted in the matrix thickness (X₁, p?=?0.0957) and PR content (X₃, p?=?0.0004) which improved the flux; conversely, NMP lacked its enhancement effect when loaded in the patch and the increase in its concentration (X₄, p?=?0.006) affected the drug permeation through human epidermis. The flux of optimal formulation was 12.7?μg/cm²/h. On the basis of the steady-state concentration and clearance of PR, the estimated patch surface was 100–120 cm², since the activity of PR is related to its Senantiomer and no in vivo bioconversion occurs.

Conclusion: A patch containing (S)-PR was prepared and the (S)-PR flux (13.3?μg/cm²/h) permitted to confirm the suitability of a transdermal administration of PR. In particular, the use of a 50?μm thick methacrylic matrix containing 8% (S)-PR and 15% NMP can allow to develop a patch non-irritating to the skin, in order to ensure a constant permeation flux of PR over 48?h.     

Fabrication and characterization of matrix type transdermal patches loaded with tizanidine hydrochloride: potential sustained release delivery system

Abstract

Objective: This study was designed to optimize and develop matrix type transdermal drug delivery system (TDDS) containing tizanidine hydrochloride (TZH) using different polymers by solvent evaporation method.

Significance: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.

Methods: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.

Results: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.

Conclusions: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.     

In vitro models to estimate drug penetration through the compromised stratum corneum barrier

Objectives: The phospholipid vesicle-based permeation assay (PVPA) is a recently established in vitro stratum corneum model to estimate the permeability of intact and healthy skin. The aim here was to further evolve this model to mimic the stratum corneum in a compromised skin barrier by reducing the barrier functions in a controlled manner. Methods: To mimic compromised skin barriers, PVPA barriers were prepared with explicitly defined reduced barrier function and compared with literature data from both human and animal skin with compromised barrier properties. Caffeine, diclofenac sodium, chloramphenicol and the hydrophilic marker calcein were tested to compare the PVPA models with established models. Results and discussions: The established PVPA models mimicking the stratum corneum in healthy skin showed good correlation with biological barriers by ranking drugs similar to those ranked by the pig ear skin model and were comparable to literature data on permeation through healthy human skin. The PVPA models provided reproducible and consistent results with a distinction between the barriers mimicking compromised and healthy skin. The trends in increasing drug permeation with an increasing degree of compromised barriers for the model drugs were similar to the literature data from other in vivo and in vitro models. Conclusions: The PVPA models have the potential to provide permeation predictions when investigating drugs or cosmeceuticals intended for various compromised skin conditions and can thus possibly reduce the time and cost of testing as well as the use of animal testing in the early development of drug candidates, drugs and cosmeceuticals.     

Formulation and rheological evaluation of ethosome-loaded carbopol hydrogel for transdermal application

Objective: To select a suitable ethosome-loaded Carbopol hydrogel formulation, specifically tailored for transdermal application that exhibits (i) plastic flow with yield stress of approximately 50–80?Pa at low polymer concentration, (ii) relatively frequency independent elastic (G′) and viscous (G″) properties and (iii) thermal stability.

Methods: Carbopol (C71, C934, C941, C971 or C974) hydrogels were prepared by dispersing Carbopol in distilled water followed neutralization by sodium hydroxide. The effects of Carbopol grade, Carbopol concentration, ethosome addition and temperature on flow (yield stress and viscosity) and viscoelastic (G′ and G″) properties of Carbopol hydrogel were evaluated. Based on the aforementioned rheological properties evaluated, suitable ethosome-loaded Carbopol hydrogel was selected. In-vitro permeation studies of diclofenac using rat skin were further conducted on ethosome-loaded Carbopol hydrogel along with diclofenac-loaded ethosomal formulation as control.

Results: Based on preliminary screening, C934, C971 and C974 grades were selected and further evaluated for flow and viscoelastic properties. It was observed that ethosome-loaded C974 hydrogel at concentration of 0.50 and 0.75% w/w, respectively, demonstrated acceptable plastic flow with distinct yield stress and a frequency independent G′ and G″. Furthermore, the flow and viscoelastic properties were maintained at the 4, 25 and 32?°C. The results from in vitro skin permeation studies indicate that ethosome-loaded C974 hydrogel at 0.5% w/w polymer concentration exhibited similar skin permeation as that of ethosomal formulation.

Conclusion: The results indicate that suitable rheological properties of C974 could facilitate in achieving desired skin permeation of diclofenac while acting as an efficient carrier system for ethosomal vesicles.     

Formulation optimization of a drug in adhesive transdermal analgesic patch

Abstract

Context: Conventional pain management approaches have limitations such as gastrointestinal side effects, frequent dosing, and difficulties in swallowing medications. Hence, to overcome these limitations, we developed a transdermal analgesic patch.

Objective: This study was designed to formulate a drug in adhesive transdermal patch with codeine (CDB) and acetaminophen (APAP) that may potentially treat moderate pain in children.

Materials and methods: Three analgesic drugs hydrocodone bitartrate, CDB and APAP were screened by a slide crystallization study using polarized light microscope and their permeation profiles were studied using vertical Franz diffusion cells across porcine ear skin, dermatomed human skin and epidermis for 24?h, and the samples were quantified by high performance liquid chromatography. Patches used for permeation studies were prepared by dissolving sub-saturation concentration of the drug(s) in adhesive (with/without 5% w/w oleic acid [OA]), cast with a film casting knife.

Results and discussion: Among the three drugs screened, CDB demonstrated the best permeation profile (660.21?µg/cm²), and shortest lag time (4.35?±?0.01?h), and hence was chosen for patch studies. The highest concentration of CDB in the patch at which drug does not crystallize was determined as 40% of its saturation solubility (Cs) and that of APAP was determined as 200% of its Cs. CDB standalone patch delivered 105.48?µg/cm² of CDB, while the CDB–APAP combination patch with 5% w/w OA delivered 151.40?µg/cm² CDB and 58.12?µg/cm² APAP in 24?h.

Conclusion: Drug-in-adhesive patches using CDB and APAP were developed for infants and children. Addition of OA enhanced solubility and permeation of drugs.     

Topical permeation characteristics of diclofenac sodium from NaCMC gels in comparison with conventional gel formulations.

Topical gel formulations of diclofenac sodium were prepared by using sodium carboxymethylcellulose (NaCMC), a low-toxicity cellulose polymer as a gel-forming material that is biocompatible and biodegradable. The influence of various formulation variables, such as initial drug concentrations and NaCMC concentration, and certain skin permeation enhancers on release characteristics of the diclofenac sodium from the prepared gels through a standard cellophane membrane was studied in comparison with four commercially available gel formulations of diclofenac sodium,. The cumulative amounts released and the apparent release rates were higher for the prepared gels in comparison with the commercial formulations. Skin permeation studies using abdominal rat skin revealed good improvement of skin permeation characteristics of diclofenac sodium using NaCMC gels as compared to the commercial gels. The cumulative amount permeated at 6 h (microg/cm2), steady-state flux Jss (microg/cm2 h), lag time tL (h), permeability coefficient kp (cm/s), partition coefficient k, and diffusion coefficient D (cm2/s) were determined for the prepared gels in comparison with the commercial gels. Skin permeation enhancers such as isopropyl alcohol (IPA), Tween 80, and alpha-tocopherol polyethylene glycol succinate (TPGS) exhibited little or no effect on the permeation characteristics of diclofenac sodium. Infrared (IR) spectrum and differential scanning calorimetry (DSC) studies on the pure diclofenac sodium, NaCMC, and their physical mixture at a 1:1 ratio revealed that there was no positive evidence for the interactions between the drug and NaCMC, indicating the compatibility of the drug and the vehicle. Based on experimental results, preparation of diclofenac sodium gels using NaCMC vehicle is promising.     

Nanocarrier-based topical drug delivery for an antifungal drug

Objective: The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin.

Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween® 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram.

Results and discussion: The maximum % transmittance obtained were 96.9?±?1.0%, 95.9?±?3.0% and 93.7?±?1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32?±?0.8 nm and –3.7?±?1.2?mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89?±?2.06 and 18.02?±?4.3?µg/cm²/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37?±?3.6?µg/cm² drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM).

Conclusion: The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach.     

Permeability and Retention Studies of (-)Epicatechin Gel Formulations in Human Cadaver Skin

ABSTRACT

(-)Epicatechin (EC) is a major antioxidant component of grape seed extract which has become increasingly popular in topical skin preparations. This study assessed the following: (1) the permeability through cellulose membranes of EC in three different gel formulations (Carbopol®940, Klucel®, and Ultrez?10); (2) the effect of three different antioxidants (butylated hydroxytoluene (BHT), alpha-tocopherol (VE), and ascorbic acid (AA)) on the stability and penetration properties of EC; and (3) the permeability and retention of EC in Ultrez?10 gels, supplemented with BHT or VE, on human cadaver skin. Permeability studies through cellulose membranes showed that different gelling agents do not significantly affect the permeability of EC (n?=?7/gel; p?>?0.05). BHT and VE have antioxidant properties superior to AA (p?<?0.05) and preserve 100% of the initial content of EC for 28 days. Permeation studies on cadaver human skin, following application of two anhydrous gel formulations (0.5% EC in Ultrez?10 containing BHT or VE), showed that EC was not detectable in the receiving solution. However, the EC amount in viable skin increased with time, indicating that EC penetrated and was retained in the upper part of the skin for approximately 1% and 3% of the dose for the formulations containing BHT and VE, respectively.     

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.     

Topical delivery of paclitaxel for treatment of skin cancer

Context: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach.

Objective: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma.

Methods: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study.

Results: The particle size distribution was found to be in the range of 78.82–587.8?nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (J_ss), permeability coefficient (K_p), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer.

Conclusion: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.     

In vitro skin permeation and anti-atopic efficacy of lipid nanocarriers containing water soluble extracts of Houttuynia cordata

Objective: The aims of this work are to enhance the in vitro skin permeation of Houttuynia cordata (water-soluble extract of H. cordata; HCWSE) and to boost the efficacy of HCWSE against atopic dermatitis (AD) – like skin lesion in hairless mice using lipid nano-carriers (liposome and cubosome).

Methods: HCWSE was obtained by a hot water extraction. Monoolein cubosomal suspension containing HCWSE and egg phosphatidylcholine liposomal suspension containing the same was prepared by a sonication and a film hydration method, respectively.

Results: The lipid nano-carriers, especially cubosome, enhanced the in vitro skin permeation of HCWSE. The inhibitory effects of HCWSE-containing lipid carrier suspensions on the development of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesion in hairless mice were investigated by observing appearance of skin surface, serum immunoglobulin E (IgE) level and cytokine expression. HCWSE-containing preparations suppressed IgE production and interleukin 4 expression, whereas they promoted interferon gamma expression. The order of lymphocyte (B-cell, Th1 cell and Th2 cell) modulating effect was HCWSE-containing cubosomal suspension?>?HCWSE-containing liposomal suspension?>?HCWSE solution in phosphate buffered saline, indicating that the cubosomal suspension, among the preparations, was the most efficacious in inhibiting the development of DNCB-induced AD-like skin lesion.

Conclusion: It is believed that the cubosomal suspension containing HCWSE would be an efficacious preparation for the treatment of AD.     

Design and Evaluation of a Lorazepam Transdermal Delivery System

Abstract

The aim of this work was to study the release and the permeation rate of lorazepam, in order to develop a transdermal therapeutic system (TTS) containing that drug. Only a small number of drugs are by themselves able to permeate the skin at a useful rate in order to achieve a therapeutic effect. The lorazepam permeation rate did not reach that value and required a skin permeation enhancer to increase the skin's permeability. Three permeation enhancers (Tween 80, sodium lauryl sulfate, and benzalkonium chloride) were investigated in two different concentrations: 1% and 5% of the amount of lorazepam. The best permeation enhancement results were obtained using benzalkonium chloride in concentration of 5%.