Skin Retention Research Articles

Implementing Central Composite Design for Developing Transdermal Diacerein-Loaded Niosomes: Ex vivo Permeation and In vivo Deposition.

Background: Niosomes are surfactant-based vesicular nanosystems that proved their efficien-cy in transdermal delivery by overcoming skin inherent anatomic barrier; startum corneum. Central com-posite design is an efficient tool for developing and optimizing niosomal formulations using fewer exper-iments.Objective: The objective of this study was to prepare niosomes as a transdermal delivery system of di-acerein using film hydration technique, employing central composite design, for avoiding its oral gastroin-testinal problems.Methods: Three-level three-factor central composite design was employed for attaining optimal niosomes formulation with the desired characteristics. Three formulation variables were assessed: amount of salt in hydration medium (X1), lipid amount (X2) and number of surfactant parts (X3). DCN-loaded niosomes were evaluated for entrapment efficiency percent (Y1), particle size (Y2), polydispersity index (Y3) and zeta potential (Y4). The suggested optimal niosomes were subjected to further characterization and utilized as a nucleus for developing elastic vesicles for comparative ex vivo and in vivo studies.Results: The values of the independent variables (X1, X2 and X3) in the optimal niosomes formulation were 0 g, 150 mg and 5 parts, respectively. It showed entrapment efficiency percentage of 95.63%, parti-cle size of 436.65 nm, polydispersity index of 0.47 and zeta potential of -38.80 mV. Results of ex vivo permeation and skin deposition studies showed enhanced skin permeation and retention capacity of the prepared vesicles than drug suspension.Conclusion: Results revealed that a transdermal niosomal system was successfully prepared and evaluat-ed using central composite design which will result in delivering diacerein efficiently, avoiding its oral problems.

Core–shell‐type polymer–lipid nanoparticles for the transdermal delivery of daidzein

Daidzein (DZ) is an ideal Chinese herb for treating cardiocerebrovascular disease. Despite its poor water solubility and limited application, DZ was successfully loaded, along with penetration enhancer azone, onto core–shell-type polymer–lipid nanoparticles through a two-step preparation method. The mean particle diameter, encapsulation efficiency, and drug-loading rate of DZ–polymer-azone–lipid nanoparticles (D-P-Azone-LNs) were 77.59 ± 2.26 nm, 79.91% ± 1.46%, and 1.50% ± 0.02%, respectively. In skin penetration experiment, the cumulative amount of DZ from D-P-Azone-LN reached 14.91 μg·cm−2 at 72 h. This amount was 1.44 and 6.01 times higher than those of DZ–polymer–lipid nanoparticles (D-P-LNs) and DZ solution, respectively. Confocal laser scanning microscopy was used to conduct a qualitative analysis. In vivo study, D-P-Azone-LN achieved better skin retention than those of D-P-LN and DZ. Furthermore, no significant irritation was observed in the skin irritation experiment. These results suggested that the core–shell polymer–lipid nanoparticles, which combined the properties of polymer and lipid nanoparticles, can offer a useful formulation for enhancing the skin permeation of drug for transdermal delivery.

Topical hydrogel patches of vinyl monomers containing mupirocin for skin injuries: Synthesis and evaluation

AbstractThe aim of this study was to formulate and evaluate acrylic acid‐based topical hydrogel patches of mupirocin for new pharmaceutical controlled release application. These cross‐linked hydrogel patches were synthesized by modified aqueous‐based polymerization technique. Acrylic acid was cross‐linked with 2‐acrylamido‐2‐methylpropanesulfonic acid (AMPS) with the help of cross‐linker N,N‐methylenebisacrylamide (MBA). Hydrogel patches were characterized by FTIR, TGA, DSC, SEM, swelling behavior, in vitro percent drug release at different pH, permeation across skin, ex vivo drug retention study, and irritation evaluation of mupirocin‐loaded hydrogels. Developed patches were spherical, thick, adhesive and with good elastic strength. FTIR confirmed the cross‐linking and formation of new structure having appropriate characteristics needed for controlled release delivery system. Dug (mupirocin) release through rabbit's skin was evaluated by Franz diffusion cell and up to 3,991.95 μg/L.5 cm2 was permeated, and drug retention in skin revealed substantial retention up to 1,261 μg/L.5 cm2. Formulated hydrogel patches were nonirritant to the skin up to 48 hr as validated by Draize patch test. Enhanced retention of drug in skin demonstrated good potential of topical delivery for skin bacterial infections.

Investigation of the enhancement effect of the natural transdermal permeation enhancers from Ledum palustre L. var. angustum N. Busch: Mechanistic insight based on interaction among drug, enhancers and skin

It has been reported that natural transdermal permeation enhancers (TPEs) are superior in safety compared with synthetic TPEs. The essential oil (EO) of Ledum palustre L. var. angustum N. Busch had a strong enhancement effect on drug skin permeation based on previous studies. However, their enhancement mechanisms and safety were still unclear. The composition of the EO was determined using GC–MS. By using donepezil (DNP) as a model drug, the enhancement effect of the constituents of the EO and the EO were evaluated by in vitro skin permeation test. Confocal laser scanning microscopy (CLSM), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and molecular docking were used to investigate the interaction among drug, enhancers and skin. Skin retention amount, apparent partition coefficient (K′) and molecular simulation were used to reflect the effect of the enhancers on drug partition into skin. The skin irritation potential was evaluated using in vivo skin erythema analysis. The results showed that the main constituents of the EO were sabinene (SA), 4-terpineol (TE), p-cymene (CY) and cuminaldehyde (CU). CU was the main active constituent of the EO, which facilitated skin permeation of DNP. CU improved the skin permeation of DNP by increasing the mobility of the stratum corneum (SC) intercellular lipids, decreasing the interaction between DNP and the SC intercellular lipids, and improving the partition of DNP into the SC layer. Besides the superior enhancement effect, CU also showed a lower skin irritation potential compared with the EO. This work gave us some enlightenment that the effectiveness and safety of the natural transdermal permeation enhancers could be improved by understanding their composition and the enhancement mechanisms.

Microemulsion and Microporation Effects on the Genistein Permeation Across Dermatomed Human Skin.

This study reports the microemulsion (ME) effects on the permeation of genistein across normal (intact) and microporated human skin. The genistein formulation was optimized to know the stable ME region in the pseudo-ternary phase diagrams and to maximize the skin permeation and retention of genistein. The phase diagrams were constructed with different oil phases, surfactants, and their combinations. The influence of formulation factors on the permeation through intact and microporated human skin was determined. Based on its wide ME region, as well as permeation enhancement effects, oleic acid was used as an oil phase with various surfactants and co-surfactants to further maximize the ME region and skin permeation. The water content in the formulation played an important role in the ME stability, droplet size, and flux of genistein. For example, the ME with 20% water exhibited 4- and 9-fold higher flux as compared to the ME base (no water) and aqueous suspension, respectively. Likewise, this formulation had demonstrated 2- and 4-fold higher skin retention as compared to the ME base (no water) and aqueous suspension, respectively. The skin microporation did not significantly increase the skin permeation of genistein from ME formulations. The ME composition, water content, and to a lesser extent the ME particle size played a role in improving the skin permeation and retention of genistein.

Antidermatophytic Activity and Skin Retention of Clotrimazole Microemulsion and Microemulsion-Based Gel in Comparison to Conventional Cream

Aim: Antifungal activity, skin permeation and skin retention of water-in-oil microemulsion (ME) and microemulsion-based gel (MBG) containing clotrimazole (CTZ) were evaluated in comparison to a conventional CTZ cream. Methods: CTZ-ME and CTZ-MBG containing 1% w/w of CTZ were produced. Antifungal activity against Trichophyton mentagrophytes was assessed by the agar diffusion method. Pig skin was used in the in vitro penetration study using modified Franz diffusion cells. Drug amounts which permeated into the receptor fluid, retained in the skin membrane and remained in the donor compartment were analyzed by a validated HPLC technique. Results: CTZ-ME and CTZ-MBG exhibited inhibition zones against T. mentagrophytes whereas the conventional cream did not reveal any inhibition zone in the assay. While no CTZ was detected in the receptor fluid up to 24 h following the in vitro penetration study from all tested formulations, the amount of CTZ retained in the skin membrane when applying CTZ-ME and CTZ-MBG was remarkably higher than that when applying the cream. Conclusion: Results revealed the capacity of ME and MBG in improving skin bioavailability of CTZ while reducing the risk of systemic side effects. Thereby, ME and MBG could increase the efficacy of CTZ for dermatophytosis treatment in comparison to conventional cream.

The Influence of Formulation and Excipients on Propranolol Skin Permeation and Retention.

The objective of this work was to study in vitro propranolol permeation and skin retention after topical application of different semisolid vehicles, with the final aim of developing new topical formulations intended for the treatment of infantile hemangioma, able to produce therapeutic drug levels in the skin, avoiding systemic absorption. Propranolol ointments, creams, and gels were prepared and tested on pig skin, an accepted model of human skin. From the results obtained in the present work it is clear that the permeation of propranolol across the skin is a poor predictor of its skin retention, at least in the time-frame considered. With an application time of 4 h, reasonably close to the permanence time of a semisolid formulation on the skin surface, the best performance (high retention and low skin penetration) was obtained with lipophilic formulations, in particular with a lipophilic cream containing olive oil. Hydrophilic formulations, such as gels, are characterized by a significant permeation across the skin, probably leading to systemic side effects, accompanied by a limited skin retention. Overall, the results obtained in the present work pose the basis for the development of new topical formulations, containing propranolol, with better performance and reduced systemic absorption.

Development and Evaluation of Ketoconazole Loaded Nano-sponges for Topical Drug Delivery

Beta-cyclodextrin nanosponges (NS) based hydrogel had been studied as a topical delivery of ketoconazole (KTZ) for effective eradication of cutaneous fungal infection. The purpose of the present study was to develop KTZ loaded NS for topical drug delivery with skin targeting to minimizing the adverse side effects and providing a controlled release. The four types of NS were synthesized by varying the molar ratios of β-cyclodextrin (β-CD) to diphenylcarbonate (DPC) as a cross linker viz. 1:2, 1:4, 1:6, and 1:8. The KTZ loaded NS shows particle size 274.6-367 nm and high loading efficacy was obtained, FTIR, DSC, XRD studies confirmed the complexation of KTZ with NS. Hydrogel were evaluated comparatively with commercial product with respect to physicochemical properties, ex-vivo skin permeation and skin retention on human cadaver skin and antifungal activity. Ex-vivo study of KTZ-NS hydrogel exhibited controlled drug release up to 8 hrs whereas skin retention studies show avoidance of the systemic uptake and better accumulative uptake of the drug compared to marketed formulation. The zone of inhibition of KTZ-NS hydrogel was higher in comparison with commercial formulation against Candida albicans. These results indicate that the KTZ-NS is having controlled drug release, potential of skin targeting with enhanced antifungal activity.

Paeonol-Loaded Ethosomes as Transdermal Delivery Carriers: Design, Preparation and Evaluation.

Paeonol exhibits a wide range of pharmacological activities, such as anti-inflammatory, antidiabetic as well as pain-relieving activities. However, its intrinsic properties, such as low water solubility, poor stability and low oral bioavailability, restrict its clinical application. The current study aimed to optimize paeonol-loaded ethosomal formulation and characterize it in terms of encapsulation efficiency (EE), vesicle size (VS), zeta potential (ZP) and polydispersity index (PDI), in addition to differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) studies. Here, paeonol-loaded ethosomes were prepared by the injection method and optimized by the single-factor test and central composite design-response surface methodology. The optimized paeonol-loaded ethosomes had an EE of 84.33 ± 1.34%, VS of 120.2 ± 1.3 nm, negative charge of −16.8 ± 0.36 mV, and PDI of 0.131 ± 0.006. Ethosomes showed a spherical morphology under the transmission electron microscope (TEM). DSC, XRD and FT-IR results indicated that paeonol was successfully incorporated into the ethosomes. In-vitro transdermal absorption and skin retention of paeonol from paeonol-loaded ethosomes were 138.58 ± 9.60 µg/cm2 and 52.60 ± 7.90 µg/cm2, respectively. With reasonable skin tolerance, ethosomes could be a promising vehicle for transdermal delivery of paeonol.

FORMULATION AND EVALUATION OF TOPICAL FORMULATION FOR CUTANEOUS TUBERCULOSIS

Cutaneous Tuberculosis is also known as dermal tuberculosis or tuberculosis cutis (extrapulmonary tuberculosis) which can occur in any age group and patients who may or may not be suffering from pulmonary tuberculosis. The current treatment given for the disease is oral therapy of anti-tubercular drugs which has many side effects such as hepatotoxicity, headache, anxiety, euphoria, insomnia, eosinophilia, hepatitis. Hence to avoid these side effects and to increase efficiency of current therapy a topical proniosomal gel of isoniazid was formulated. Coacervation phase separation method was used and proniosomal gel was formulated by using Span 20, soya lecithin, and cholesterol. Optimum concentration of 3 factors Span 20, soya lecithin, and cholesterol were determined using Box Behnken design with at 2 levels and vesicle size and entrapment efficiency as responses. The optimized proniosomal gel was characterized by vesicle size, entrapment efficiency, transmission electron microscopy (TEM), in vitro drug release, skin retention studies, skin irritation studies and stability studies. The optimised batch showed vesicle size of 2.27±1.82 µ, and entrapment efficiency of 98.15±0.25 %. The optimised formulation was stable under refrigeration condition (5°C) in amber coloured bottle, was non-irritating and showed 98.10±1.28 % release and 85±1.53 % permeation after 6 h and 436±12 µg drug was retained in the skin after 3 hrs. Keywords: Cutaneous tuberculosis, isoniazid, proniosomal gel, stabilityÂ

Nanostructured gel for topical delivery of azelaic acid: Designing, characterization, and in-vitro evaluation

The study is designed to formulate, optimize and evaluate Azelaic acid loaded nano-structured lipid carrier (NLCs) with an aim to enhance its skin targeting, retention, and achieve sustained release with reduced drug related side effects. NLCs were formulated by melt emulsification and ultra-sonication technique and optimized employing 33 full factorial design taking lipid:drug ratio, surfactant concentration and sonication time as independent variables with particle size (PS) and entrapment efficiency (EE) as dependent variables. The optimized formulation (F23) exhibited spherical surfaced stable nano particles of 49.6 ± 1.24 nm size and 83.4 ± 2.14% EE. Formulation F23 was then incorporate to aloe-vera based carbopol gel and evaluated for its physiological properties, drug content, in-vitro release and skin distribution (fluorescent microscopy) analysis. The gel was found to be non-irritating, homogenous, with optimum moisture content, spreadability and occlusivity. In-vitro permeation studies showed NLC preparation to markedly enhance the dug's skin retention in comparison to drug suspended in gel and marketed preparation. The skin distribution studies employing rhodamine 6G further confirmed the permeation of NLCs to the deeper layers of skin. The experimental findings suggested that NLCs could serve as a promising carrier for site specific targeting with better skin retention abilities.

Improvement of cutaneous delivery of methylene blue by liquid crystals

The purpose of this study was to evaluate the effect of composition and characteristics of liquid crystalline phases (LCPs) on cutaneous delivery of methylene blue (MB). LCPs were obtained by mixing Brij97® with water at various ratios; Brij97®:water at 8:2 (F8:2), 7:3 (F7:3), and 6:4 (F6:4) were selected, and MB was incorporated at 0.1%. F8:2 and F7:3 exhibited textures and small angle X-ray scattering (SAXS) patterns corresponding to lamellar phase, whereas F6:4 displayed characteristics of hexagonal phase. All three LCPs were stable for 9 months, and exhibited thixotropic pseudoplastic behaviour. Increasing water content increased viscosity. All three LCPs released less (3.2- to 6.6-fold) MB than control gel (3.0% hydroxyethylcellulose (HEC) + 0.1% MB), demonstrating their ability to sustain release. Despite the lower release, all LCPs improved skin retention of MB at 6 h post-application (1.3- to 2.1-fold) compared to the control gel. Among the LCPs, F8:2-mediated skin retention of MB was more pronounced, followed by F7:3. Consistent with the increased penetration, transepidermal water loss (TEWL) also increased after treatment with the LCPs (2.0–2.8 fold), which suggests their influence on skin barrier. Irritation studies by Hen’s Egg Test – Chorioallantoic Membrane (HET-CAM) suggest that F7:3 and F6:4 may be better tolerated by the skin than F8:2.

Dermal delivery of Fe-chlorophyllin via ultradeformable nanovesicles for photodynamic therapy in melanoma animal model

Melanoma is resistant to chemotherapeutics with poor prognosis and high potential of metastasis. Photodynamic therapy (PDT) represents a localized therapeutic modality, as cytotoxicity occurs when light activates photosensitizer (PS) at the tumour site. The aim of this study is dermal delivery of a high molecular weight hydrophilic photosensitizer (PS), ferrous chlorophyllin (Fe-CHL) via transethosomes for treatment of melanoma by PDT.Transethosomes were made of phosphatidyl choline, edge activator and 20% w/v Ethanol. They were evaluated for mean size, zeta potential, entrapment efficiency, ex-vivo permeation, localization in skin layers by transmission electron microscope (TEM), and finally, evaluated in melanoma animal model. Transethosomes of different mean vesicle size were evaluated for their skin retention and permeation through mice skin. TE of ∼500 nm (E3) being ultradeformable showed deep localization in skin confirmed by ex-vivo and TEM micrographs without permeation of PS to recipient compartment due to its size.The proposed study offers successful treatment of resistant melanoma by PDT, where complete tumour regression of small tumours occurred after single PDT, while large tumours after double PDT without recurrence for 8 months. This indicates the efficiency of nanovesicles in PS delivery and the efficiency of Fe-CHL in production of reactive oxygen species.

Flutamide-Loaded Zein Nanocapsule Hydrogel, a Promising Dermal Delivery System for Pilosebaceous Unit Disorders.

Zein is a naturally occurring corn protein having similarity to skin keratin. Owing to its hydrophobicity and biodegradability, zein nanocarriers are promising drug delivery vehicles for hydrophobic dermatological drugs. In this study, zein-based nanocapsules (ZNCs) were exploited for the first time as dermal delivery carriers for flutamide (FLT), an antiandrogen used for the management of pilosebasceous unit disorders. FLT-loaded ZNC of appropriate particle size and negative surface charge were prepared by nanoprecipitation method. The dermal permeation and skin retention of FLT from ZNCs were studied in comparison to corresponding nanoemulsion (NE) and hydroalcoholic drug solution (HA). ZNCs showed a significantly lower permeation flux compared to NE and HA while increasing the skin retention of FLT. Confocal laser scanning microscopy (CLSM) demonstrated the follicular localization of the fluorescently labeled NCs. The incorporation of NCs in chitosan gel or Carbomer® 934 gel was studied. Carbomer® gel increased the skin retention of FLT compared to chitosan gel. Accordingly, Carbomer® hydrogel embedding FLT-loaded ZNCs is a promising inexpensive, biocompatible dermal delivery nanocarrier for localized therapy of PSU disorders suitable for application on oily skin.

Hyaluronic acid decorated tacrolimus-loaded nanoparticles: Efficient approach to maximize dermal targeting and anti-dermatitis efficacy

Nano-delivery systems have gained remarkable recognition for targeted delivery of therapeutic payload, reduced off-target effects, and improved biopharmaceutical profiles of drugs. Therefore, we aimed to fabricate polymeric nanoparticles (NPs) to deliver tacrolimus (TCS) to deeper layers of the skin in order to alleviate its systemic toxicity and improved therapeutic efficacy against atopic dermatitis (AD). To further optimize the targeting efficiency, TCS-loaded NPs were coated with hyaluronic acid (HA). Following the various physicochemical optimizations, the prepared HA-TCS-CS-NPs were tested for in vitro drug release kinetics, drug permeation across the stratum corneum, percentage of drug retained in the epidermis and dermis, and anti-AD efficacy. Results revealed that HA-TCS-CS-NPs exhibit sustained release profile, promising drug permeation ability, improved skin retention, and pronounced anti-AD efficacy. Conclusively, we anticipated that HA-based modification of TCS-CS-NPs could be a promising therapeutic approach for rationalized management of AD, particularly in children as well as in adults having steroid phobia.

Is Vitamin D3 Transdermal Formulation Feasible? An Ex Vivo Skin Retention and Permeation.

Vitamin D3 supplementation is important to prevent and treat hypovitaminosis that is a worldwide public health issue. Most types of supplementation are by oral route or fortification foods. The alternative route must be investigated, as transdermal route, for people with fat malabsorption or other diseases that impair the absorption of vitamin D3. This study focused on verifying the feasibleness of vitamin D3 skin retention and permeation with the presence of chemical penetration enhancers (soybean lecithin, isopropyl palmitate, propylene glycol, ethoxydiglycol, and cereal alcohol) at different pharmaceutical forms (gel and cream) through a human skin. The integrity of skin was evaluated by transepidermal water loss (TEWL) during the skin retention and permeation test. The combination of chemical penetration enhancers presented in cream did not compromise the skin, different from the gel that association of cereal alcohol and propylene glycol compromised the skin in 24h. Gel formulation showed vitamin D3 detection at stratum corneum in 4h and at epidermis and dermis in 24h. Vitamin D3 demonstrated an affinity with the vehicle in the cream formulation and was detected at the skin surface. No active was found at receptor fluid for both formulations. In conclusion, the vitamin D3 did not indicate feasibleness for transdermal use probably due to its physical-chemical characteristics such as high lipophilicity since it was not permeated through a human skin. Nevertheless, the transdermal route should be continuously investigated with less lipophilic derivates of vitamin D3 and with different combination of penetration enhancers.

Comparative behavior between sunscreens based on free or encapsulated UV filters in term of skin penetration, retention and photo-stability

BackgroundThe growing incidence of photodamaging effects caused by UV radiation (e.g. sunburn, skin cancer) has increased the attention from health authorities which recommend the topical application of sunscreens to prevent these skin damages. The economic stakes for those companies involved in this international market are to develop new UV filters and innovative technologies to provide the most efficient, flexible and robust sunscreen products. Today the development of innovative and competitive sunscreen products is a complex formulation challenge. Indeed, the current sunscreens must protect against skin damages, while also being safe for the skin and being sensory and visually pleasant for the customers when applied on the skin. Organic UV filters, while proposing great advantages, also present the risk to penetrate the stratum corneum and diffuse into underlying structures with unknown consequences; moreover, their photo-stability are noted thorny outcomes in sunscreen development and subsequent performance. In recent years, the evaluation of the interaction between skin and sunscreen in terms of penetration after topical application has been considered from European authority but still its testing as their photo-stability assessment are not mandatory in most countries. ObjectiveThis study, based on in-vitro approaches, was performed to evaluate and compare the retention and the penetration of organic UV filters in free or encapsulated form inside the skin as well as their respective photo-stability. MethodsSunscreen formulation with a combination of Avobenzone and Octocrylene in “free form” and a formulation using the same UV filters but encapsulated in a sol-gel silica capsule, were analyzed and compared by FTIR Imaging Spectroscopy. Tape stripping method was used to investigate the penetration of these UV filters inside the stratum corneum. Their photo-stabilities were evaluated by spectroscopic measurements (FTIR, UV/Vis) and standard measurements were calculated: AUC (Area Under the Curve) and SPF (Sun Protection Factor). ResultWith traditional formulation, the organic UV filters penetrated significantly into the stratum corneum while the same UV filters combined with encapsulation technology remained on the skin surface. The encapsulation technology also improved significantly their stability. ConclusionEncapsulation technology is a promising strategy to improve the efficacy of sunscreen product using organic UV filters and to reduce safety problem. On the other hand, this study highlighted the pertinence of the FTIR Spectroscopy to test, compare and investigate sunscreen formulations.

Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and MelanomaCells.

5-Fluorouracil delivery profiles in the form of chitosan-folate submicron particles through skin and melanoma cells invitro were examined using microwaves as the penetration enhancer. The invivo pharmacokinetic profile of 5-fluorouracil was also determined. Chitosan-carboxymethyl-5-fluorouracil-folate conjugate was synthesized and processed into submicron particles by spray-drying technique. The size, zeta potential, morphology, drug content, and drug release, as well as skin permeation and retention, pharmacokinetics, invitro SKMEL-28 melanoma cell line cytotoxicity, and intracellular trafficking profiles of drug/particles, were examined as a function of skin/melanoma cell treatment by microwaves at 2,450 MHz for 5+ 5 minutes. The level of skin drug/particle retention invitro and invivo increased in skin treated by microwaves. This was facilitated by the drug conjugating to chitosan and microwaves fluidizing both the protein and lipid domains of epidermis and dermis. The uptake of chitosan-folate particles by melanoma cells was mediated via lipid raft route. It was promoted by microwaves, which fluidized the lipid and protein regimes of the cell membrane, and this increased drug cytotoxicity. Invivo pharmacokinetic study indicated skin treatment by microwave-enhanced drug retention but not permeation. The combination of microwaves and submicron particles synergized skin drug retention and intracellular drug delivery.

Nanoemulsion containing 8-methoxypsoralen for topical treatment of dermatoses: Development, characterization and ex vivo permeation in porcine skin

Oral therapy with 8-methoxypsoralen (8-MOP) may cause major side effects, whereas the topical treatment might not be much effective due to the low penetration induced by typical formulations. Therefore, the objectives of this work are the development and characterization of a nanoemulsion (NE) containing 8-MOP together with an ex vivo permeation study, monitored by a validated HPLC-Fluo method, to determine the amount of drug retained in viable skin (epidermis (E) and dermis (D)) and in stratum corneum (SC). The optimized conditions for NE formulation were achieved by full factorial designs (25 and 32): 60 s and 60% of ultrasound time and potency, respectively; 10 mL of final volume; 2% v/v of oil phase (clove essential oil); and 10% m/v of Poloxamer 407. The NE showed mean droplet diameter of 24.98 ± 0.49 nm, polydispersity index (PDI) of 0.091 ± 0.23, pH values of 6.54 ± 0.06, refractive index of 1.3525 ± 0.0001 and apparent viscosity of 51.15 ± 3.66 mPa at 20 °C. Droplets with nanospherical diameters were also observed by transmission electron microscopy (TEM). Ex vivo permeation study showed that 8.5% of the applied 8-MOP dose permeated through the biological membranes, with flux (J) of 1.35 μg cm−2 h−1. The drug retention in E + D and in SC was 10.15 ± 1.36 and 1.95 ± 0.71 µg cm−2, respectively. Retention in viable skin induced by the NE was almost two-fold higher than a compounded cream (5.04 ± 0.30 μg cm−2). These results suggested that the developed NE is a promising alternative for 8-MOP topical therapy when compared to commercial formulations.

Topical delivery of anthramycin II. Influence of binary and ternary solvent systems

Anthramycin (ANT) is a member of the pyrolobenzodiazepine family and is a potent cytotoxic agent. Previously, we reported the topical delivery of ANT from a range of solvents that may also act as skin penetration enhancers (SPEs). The skin penetration and uptake was monitored for simple solutions of ANT in propylene glycol (PG), dipropylene glycol (DiPG), Transcutol P (TC), isopropyl myristate (IPM), propylene glycol monocaprylate (PGMC) and propylene glycol monolaurate (PGML). The amounts of PG, DiPG and TC that were taken up by, and that penetrated the skin were also measured, with a clear dependence of ANT penetration on the rate and extent of PG and TC permeation. The present work investigates ANT skin delivery from a range of binary and ternary systems to determine any potential improvement in skin uptake compared with earlier results for the neat solvents. Following miscibility and stability studies a total of eight formulations were taken forward for evaluation in human skin in vitro. Binary systems of PG and water did not result in any skin permeation of ANT. Combining PG with either PGMC or PGML did promote skin penetration of ANT but no significant improvement was evident compared with PG alone. More complex ternary systems based on PG, DiPG, PGMC, PGML and water also did not show significant improvements on ANT permeation, compared with single solvents. Total skin penetration and retention of ANT ranged from 1 to 6% across all formulations studied. Where ANT was delivered to the receptor phase there were also high amounts of PG permeation with >50% and ~35% PG present for the binary systems and ternary vehicles, respectively. These findings along with our previous paper confirm PG as a suitable solvent / SPE for ANT either alone or in combination with PGML or PGMC. The results also underline the necessity for empirical testing to determine whether or not a vehicle is acting as a SPE for a specific active in a topical formulation.