Membranas de quitosana para uso em sistema de liberação controlada de insulina: síntese e caracterização.

Abstract

Diabetes Mellitus (DM) accounts for a set of metaboiic disorders characterized by chronic hyperglycemia resulting from failure of insulin action and/or insulin secretion. Insulinotherapy consists in treating DM through daily subcutaneous applications of insulin to control glycemic leveis. Chitosan, studied by Biomedicine, is a biomaterial that can be used in pharmacol-controlled delivery systems whose delivery rate can be controlled by sodium tripolyphosphate (TPP) - an ionic reticulate chitosan used in specific applications. Thus, the primary objective of this work was to develop and estimate chitosan polymeric membranes and reticulated chitosan through TPP to be used in insulin-controlled delivery system, aiming to obtain an alternative route rather than the injectable system to administer this drug. The existing membranes were characterized by Surface Tension techniques, Fourier Transform Infrared-Region Spectroscopy (FTIR), X-ray Diffraction (XRD), Optic Microscopy (OM), Scanning Electron Microscopy (SEM), Energy-dispersive X-ray Spectroscopy (EDX), HighPerformance Liquid Chromatography (HPLC), Enzymatic Biodegradation, Macrophage Cellular Availability Estimate (MCA), and Nitric Oxide Production Determination. The surface tension measurements enabled to detect an increase in the hydrophilic character of the surface membrane containing insulin and tripolyphosphate compared to those of pure chitosan. The FTIR helped to identify interaction between chitosan, insulin and tripolyphosphate. The XRD technique showed a change in chitosan semicrystalline character with insulin and tripolyphosphate. Chemical elements in chitosan, insulin and tripolyphosphate sodium were detected by EDX technique. OM and SEM revealed a change in the membrane morphology with insulin when compared to that of pure chitosan in the presence of granular multiple-sized particles. The HPLC test showed that the insulin was identified and separated without any structural change in chitosan membrane even when this membrane was reticulated by TPP. The biodegradation tests revealed that the membranes are biodegradable. Composite biocompatibility was confirmed by MCA and NO that revealed little or no citotoxity. The results presented indicated changes that suggest the presence of insulin incorporated in chitosan membrane. The membranes developed presented availability to be used as biomaterial in insulin-controlled delivery systems.