Combined effect of polymeric nanocapsules and chitosan hydrogel on the increase of capsaicinoids adhesion to the skin surface.

Abstract

This work explored the effect of the encapsulation in polymeric nanocapsules, as well as of the incorporation of such nanoparticles in a chitosan hydrogel, on the skin adhesion and skin penetration/permeation of capsaicinoids (capsaicin and dihydrocapsaicin), which are used as topical analgesic to treat chronic pain. The skin experiments were performed using a modified (drug adhesion and drug diffusion) and a normal Franz diffusion cell (drug diffusion) with porcine skin as membrane. The AUC0-h of the washability profile (% washed away vs. time) determined for the formulation combining both factors studied (chitosan hydrogel containing drug-loaded nanocapsules) was 198.88 +/- 10.05/153.53 +/- 5.99, for capsaicin and dihydrocapsaicin respectively, significantly lower than the values observed for the chitosan hydrogel containing free drug (291.57 +/- 3.83/278.18 +/- 5.28) and for the hydroxyethyl cellulose containing drug-loaded nanocapsules (245.47 +/- 13.18/197.69 +/- 15.78). By adequate fitting to the monoexponential first order equation, the washing rate values indicated that the nanocapsules were more efficient in increasing the drugs skin adhesion than the chitosan gel. Regarding the skin penetration/permeation study, after washing the skin, the formulation which presented the lowest washing rate (chitosan gel containing nanocapsules) was the one which led to a higher amount of capsaicinoids in the skin layers (epidermis and dermis). Without washing the skin, the nanoencapsules caused retention of the drugs in the outer skin layer (epidermis). In conclusion, the skin adhesion of the nanocapsules and their capability of controlling the drug diffusion were shown. Combining chitosan gel to nanocapsules led to a formulation of great skin bioadhesion.