Dispositivo a base de quitosana para liberação controlada de insulina visando uma rota não convencional de administração.

Abstract

In this study, chitosan-based devices (membranes and beads) were developed aiming insulin encapsulation for the administration by an unconventional route. Chitosan membranes were prepared and the influence of the processing method (freeze-drying and solvent evaporation), the type of solvent used to dissolve the chitosan (acetic or lactic acids), and whether or not neutralization was applied in the chitosan/insulin interactions were evaluated using Fourier Transform Infrared Spectroscopy (FTIR). The type of processing and the use or not of neutralization affected the chitosan/insulin interaction properties. Regardless the type of acid, interactions between chitosan and insulin were only possible for membranes prepared through solvent evaporation with prior chitosan solution neutralization. However, membranes prepared with acetic acid were brittle and those prepared with lactic acid strongly adhered to the Petri dishes. Thus, chitosan solutions solubilized in acetic or lactic acid and then neutralized were used to produce chitosan beads through the ionotropic gelation method using sodium tripolyphosphate (TPP) and carboxymethylchitosan (CMC) as a gelling solution. The beads were characterized by FTIR, optical microscopy (OM), swelling degree, water solubility, and moisture content. Interaction between chitosan and insulin was recorded for all beads (FTIR). However, effective cross-linking was only verified for beads prepared with TPP. According to OM images, the TPP prepared beads showed more uniform, rounded, and less porous contours, especially those prepared with lactic acid solutions. The swelling degree, moisture content, and water solubility were greater for the beads prepared with lactic acid and cross-linked with TPP. They were, thereby, subject to the encapsulation effectiveness, in vitro release, and release kinetics tests. There was good encapsulation efficiency (74.36%) although the cumulative percentage release in 48 h was considered low (16.8%). The release process in vitro kinetics used was the Peppas-Sahlin model, controlled both by the diffusion and the relaxation of the polymer chains or swelling degree. In general, these findings demonstrate that these beads can be a promising insulin carrier for future clinical application through an unconventional route of administration.