Desenvolvimento de nanocápsulas contendo ácido retinóico pata tratamento tópico da acne

Abstract

Acne vulgaris is a frequent condition affecting about 80 percent of teenagers in the world. According to the evolution, acne is classified as mild, moderate or severe. Retinoic acid (tretinoin; RA) is the first choice for patients with mild to moderate acne. Nevertheless, topicalapplication of RA is followed by a high incidence of adverse affects: local irritation such as erythema, peeling and burning at the application site and increased susceptibility to sunlight. Strategy for the new formulations is modifying local bioavailability, controlling RA release through polymers, and promoting follicular targeting resulting in more efficient treatment withreduced side effects. Nanocapsules (NC) representing an interesting alternative for controlled release, as well as for their capacity to target the pilosebaceous unit. NC has high entrapment efficiency for lipophilic drugs, as RA (log P = 4.6), low polymer content and low inherent toxicity. The aim of this work was the preparation, characterization and investigation of the release profile and cutaneous permeation of the RA-loaded NC. NC containing RA was prepared by nanoprecipitation method. NC were characterized for size, homogeneity (IP) and zeta potential using a Zetasizer 3000HS. The external morphology was evaluated by atomic force microscopy (AFM). The in vitro release studies were evaluated through Teflon (0.45 ìm) and Nylon (0.22 ìm) membranes, using Franz diffusion cells. Encapsulation efficiency of RA in NC was high (~90%). The average diameter, calculated by photon correlation spectroscopy (PCS), ranged from 218 to 318nm (blank NC) and from 219 to 281nm (RA-loaded NC). The zeta potential ranged from 31.5 to 44.0 mV (blank NC) and from 26.0 to 50.0 mV (RA-loaded NC). Blank NC maintained the physicochemical stability after 30 days of storage at 25oC, however RA-loaded NC was not able to prevent RA degradation (reduction of 40% in drug concentration was observed after 30 days). RArelease from a nanocapsule (NC) was higher than that observed for drug solution and minor that observed for Nanoemulsion (NE). The low release from solution was due to evaporation of ethanol and precipitation of RA in donor compartment. The polymer present in the interface of the NC provided controlled release of the RA. The permeation studies conducted in dermatomated pig ear skin were performed for 8h according to the clinical application time. It indicated that RA was not found in receptor chambers from NC and NE. The alcoholicsolution containing RA permeated the skin. This might be due to the significant penetration enhancement effect of ethanol and propylene glycol. It is concluded that the NC formulation can avoid the systemic uptake of tretinoin in comparison with the control and NC present apotential to avoid the systemic adverse side effect. These results indicate that RA-loaded NC with skin targeting may be a promising carrier for topical application of tretinoin controlling release system and avoiding adverse effects.