Desenvolvimento e avaliação biológica de preparações nanoestruturadas de desonida para uso tópico

Abstract

Topical corticosteroid are widely used in dermatology. However, the therapy with these drugs has some limitations related to the treatment duration and to drug potency, that may cause undesirable effects. Nanoparticulate systems have been considered alternatives for the drug control release, targeting to the specific site of action and reducing the adverse effects. In this context, the objective of this study was to prepare nanotechnologic-based semisolid formulations containing desonide, aiming to obtain applicable formulations for the treatment of dermatological diseases. Polymeric nanocapsule suspensions were prepared, employing the polymer Eudragit® RL 100, açai oil (AO) or medium chain triglycerides (MCT) as oily core and the drug at 0.25 mg mL-1 . Formulations containing AO presented mean particle size of 165 nm, and those prepared with MCT mean particle size around 131 nm. Both showed polidispersity index (PDI) < 0.2, acid pH, drug content near to the theoretical value, encapsulation efficiency of 81% and positive zeta potential. Direct exposure of the nanocapsule suspensions to UVA and UVC radiations showed that the colloidal systems were effective in protecting desonide from photodegradation and that the formulations containing açai oil presented greater photostability. In vitro phototoxicity study indicated that at concentration of 0.5 mg mL-1 , formulations did not present phototoxic potential in 3T3 murine fibroblasts and human keratinocytes using MTT and NRU cell viability assays. The nanostructured hydrogels were prepared by dispersing the Amigel® polymer (sclerotium gum) directly into the colloidal suspensions. Semisolids presented pH compatible with topical application, drug content around 0.25 mg mL-1 , and maintained the nanostructures. Regarding the flow properties, hydrogels presented non-Newtonian pseudoplastic flow, according to Ostwald model. The skin permeation/penetration study with the nanostructured hydrogels showed the drug reached the site of action of topical corticosteroids. Biological activity of the preparations was evaluated using a croton oil-induced dermatitis model and indicated that the nanostructured hydrogels had comparable effect to the commercially available formulation of desonide.