Desenvolvimento, caracterização físico-química e avaliação da eficiência de encapsulação de nanocápsulas poliméricas contendo tacrolimus

Abstract

Tacrolimus (TAC) is a macrolide lactone belonging to calcineurin inhibitor group, with topical immunomodulatory action in cases of atopic dermatitis, psoriasis and vitiligo. The topical application of TAC does not produce a significant side effects, but the sensation of transient burning, hot flashes at the application site and the pruritus lead to decrease treatment adhesion. Therefore, the development of drug delivery systems can be outlined to enhance skin permeation and reduce the topically applied, dose have been formulated to minimize side effects and maintain therapeutic efficacy. In this sense, this work aims to develop and evaluate TAC-loaded polymeric nanoparticles using poly(ԑ-caprolactone) polymer by interfacial polymer deposition method, altering the drug concentration between 0.1 and 5 mg/mL. The polymeric systems were characterized by morphological, spectroscopic and thermal studies. The physicochemical stability of the formulations was evaluated in a period up to 120 days. The analytical method for determination of TAC in these formulations was validated as recommended by Agência Nacional de Vigilância Sanitária and The International Conference on Harmonization. The stability of the drug against acid and alkaline hydrolysis was also investigated. TAC-loaded polymeric nanocapsules were successfully prepared by the chosen method. The nanoparticulate systems presented spherical shape with a smooth and regular surface and average particle size of approximately 250 nm, polydispersion index below 0.3 and zeta potential over -30 mV. X-ray diffraction confirmed that the encapsulation method was efficient and the drug primarily is in molecular dispersion in the nanocapsule oil nucleus. Raman and Fourier transform infrared spectra ensured that nanocapsulation process did not result in chemical bonds between TAC and polymer. The polymeric nanocapsules were stable for up to 90 days, where changes in pH and zeta potential began to change significantly. The formulations presented encapsulation efficiency higher than 96%, and the analytical method used proved to be selective, linear for suggested range, accurate, precise and robust, being able to quantify the nanoencapsulated TAC in the polymeric systems, providing reliable results. About hydrolisis assays, was possible to observe that TAC was susceptible to degradation in both medium, but being more stable in the acid medium. With this, the results provide an experimental basis for formulations both as a viable topical and alternative administration strategy, which may appear as an alternative to the commercial form currently employed.