Skin permeation of hydrophobic drugs loaded into polymeric nanoparticles

摘要

Polymeric nanoparticles have been employed for topical pharmaceutical applications due to its capacity to carry drugs across the skin. Biocompatible polymers are extensively applied as coating nanoparticles allowing them to present controlled physical and chemical characteristics. The proposal of this work was to evaluate the skin permeation of polymeric nanoparticles loading hydrophobic drugs. The emulsion/diffusion process was applied to produce nanocapsules composed by poly(ε-caprolactone, PCL) and PEO-PPO-PEO triblock copolymers (Pluronic~®), this process promotes the nanoencapsulation of drugs into oil core from pre-formed polymer precipitation. The organic phase was comprised of polymers (Pluronic F127 and PCL), oil, Nile red fluorophore, and hydrocortisone acetate as hydrophobic drug model, solubilized in ethyl acetate. The aqueous phase was comprised of distilled water saturated with ethyl acetate and Tween 20 surfactant. The organic phase was transferred into the aqueous phase under ultrahigh agitation (7,000 rpm), the emulsion formed was immediately transferred to a stirred reactor, the dilution phase (water and Tween~® 20) was added and then the solvent was extracted under vacuum pressure. The in vitro skin permeation of nanoparticles containing the fluorophore Nile red was evaluated by a vertical diffusion cell employing pig ear skin. The study covered the steps of preparation of animal membrane; monitoring the permeation into vertical diffusion vessel (Franz cell) up to 8 hours; preparation of histological sections into cryomicrotome; and visualization of fluorescence by confocal laser microscopy. It was possible to verify the location of polymeric nanoparticles containing the Nile red fluorophore encapsulated in presence or absence of hydrocortisone drug. It was observed that after two hours, the permeation of the particles was very low. However, for a more prolonged exposure (8 hours) was observed the deposition of the particles in the outer layers of the skin (stratum corneum and epidermis) as well as in hair follicles. These data show that the produced nanoparticles perform the delivery of the drug in the superficial skin layers, fulfilling the role of topical application.