Thus, VChNP may be useful for effective pulmonary delivery with improved bioavailability. Such chitosan-coated nanoparticles may open up a new avenue for efficacious treatment of lung-fungal infection.

The study aimed at comparing the influence of direct and indirect skin hydration as well as massage on the dermal penetration efficacy of active compounds. Nile red was used as a lipophilic drug surrogate and was incorporated into Vaseline (petroleum jelly). The formulation was applied with and without massage onto either dry skin or pre-hydrated, moist skin. It was expected that the occlusive properties of Vaseline in combination with massage and enhanced skin hydration would cause a superposition of penetration-enhancing effects, which should lead to a tremendous increase in the dermal penetration efficacy of the lipophilic drug surrogate. Results obtained were diametral to the expectations, and various reasons were identified for causing the effect observed. Firstly, it was found that Vaseline undergoes syneresis after topical application. The expulsed mineral oil forms a film on top of the skin, and parts of it penetrate into the skin. The lipophilic drug surrogate, which is dissolved in the mineral oil, enters the skin with the mineral oil, i.e., via a solvent drag mechanism. Secondly, it was found that massage squeezes the skin and causes the expulsion of water from deeper layers of the SC. The expulsed water can act as a water barrier that prevents the penetration of lipophilic compounds and promotes the penetration of hydrophilic compounds. Based on the data, it is concluded that dermal penetration is a complex process that cannot only be explained by Fick’s law. It is composed of at least three different mechanisms. The first mechanism is the penetration of active ingredients with their solvents into the skin (convection, solvent drag), the second mechanism is the penetration of the active ingredient via passive diffusion, and the third mechanism can involve local penetration phenomena, e.g., the formation of liquid menisci and particle-associated penetration enhancement, which occur upon the evaporation of water and/or other ingredients from the formulation on top of the skin.

Aspasomes of methotrexate with antioxidant, ascorbyl palmitate, were developed and optimized using factorial design by varying parameters such as lipid molar ratio, drug to lipid molar ratio, and type of hydration buffer for transdermal delivery for disease modifying activity in rheumatoid arthritis (RA). Aspasomes were characterized by drug-excipients interaction, particle size analysis, determination of zeta potential, entrapment efficiency, and surface properties. The best formulation was loaded into hydrogel for evaluation of in vitro drug release and tested in vivo against adjuvant induced arthritis model in wistar rats, by assessing various physiological, biochemical, hematological, and histopathological parameters. Optimized aspasome formulation exhibited smooth surface with particle size 386.8 nm, high drug loading (19.41%), negative surface potential, and controlled drug release in vitro over 24 h with a steady permeation rate. Transdermal application of methotrexate-loaded aspasome hydrogel for 12 days reduced rat paw diameter (21.25%), SGOT (40.43%), SGPT (54.75%), TNFα (33.99%), IL β (34.79%), cartilage damage (84.41%), inflammation (82.37%), panus formation (84.38%), and bone resorption (80.52%) as compared to arthritic control rats. Free methotrexate-treated group showed intermediate effects. However, drug-free aspasome treatment did not show any effect. The experimental results indicate a positive outcome in development of drug-loaded therapeutically active carrier system which presents a non-invasive controlled release transdermal formulation with good drug loading, drug permeation rate, and having better disease modifications against RA than the free drug, thereby providing a more attractive therapeutic strategy for rheumatoid disease management.

Abstract. Delivering diclofenac diethylamine transdermally by means of a hydrogel is an approach to reduce or avoid systemic toxicity of the drug while providing local action for a prolonged period. In the present investigation, a process was developed to produce nanosize particles (about 10 nm) of diclofenac diethylamine in situ during the development of hydrogel, using simple mixing technique. Hydrogel was developed with polyvinyl alcohol (PVA) (5.8% w/w) and carbopol 71G (1.5% w/w). The formulations were evaluated on the basis of field emission scanning electron microscopy, texture analysis, and the assessment of various physiochemical properties. Viscosity (163-165 cps for hydrogel containing microsize drug particles and 171-173 cps for hydrogel containing nanosize drug particles, respectively) and swelling index (varied between 0.62 and 0.68) data favor the hydrogels for satisfactory topical applications. The measured hardness of the different hydrogels was uniform indicating a uniform spreadability. Data of in vitro skin (cadaver) permeation for 10 h showed that the enhancement ratios of the flux of the formulation containing nanosize drug (without the permeation enhancer) were 9.72 and 1.30 compared to the formulation containing microsized drug and the marketed formulations, respectively. In vivo plasma level of the drug increased predominantly for the hydrogel containing nanosize drug-clusters. The study depicts a simple technique for preparing hydrogel containing nanosize diclofenac diethylamine particles in situ, which can be commercially viable. The study also shows the advantage of the experimental transdermal hydrogel with nanosize drug particles over the hydrogel with microsize drug particles.

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