Aplicações de goma arábica modificada no desenvolvimento de hidrogéis para uso como dispositivos de liberação modificada de fármaco

Abstract

Development of polysaccharide-based hydrogels emerges as alternative for applications on modified drug release because the polysaccharides are often biodegradable and non-toxic. In this research, the Arabic gum (AG) was used for obtainini hydroiels matrices. Raw AG is not able to form hydrogel but if chemically modified by reaction with glycidyl methacrylate (GMA), for instance, it can form hydrogel just by cross-link of vinyl groups. Such reaction consists in partial or total insertion molecules of GMA to the AG structure. In this study, the different coupling of that reaction were accomplished through the reaction of GMA with poly(acrylic acid) (PAAc) or poly(vinyl alcohol} (PVA) in different pHs aqueous solutions and the respective products were characterized by use of NMR (1H and 13C} and FTIR techniques. It was find that the different pathways for coupling of GMA to hydroxyl groups of PVA and carboxyl groups of PAAc are dependent of the pH of the solution and that they occur, at most, through GMA epoxy-ring opening. In addition, three formulations of hydrogels based on modified Arabic gum (AGm) were developed. The hydrogels from first one are constituted exclusively by cross-linked AGm and do not have good mechanical properties because they easily broken during the drying and purification stages. The hydrogels from the other two formulations are constituted by AGm and desired amounts of N,N-dimethyl acrylamide (DMAAm) and methacrylic acid (AcMet) monomers copolymerized/cross-linked in aqueous solution. These hydrogels presented good mechanical properties and were characterized through FTIR spectroscopy and by the swelling measurements done in different pHs and ionic strength. The equilibrium-swelling index of AGm-co-DMAm-AcMet hydrogels depends of pH and ionic strength conditions, so they were classified as stimuli-responsive hydrogels. The potential of uses of those smart hydrogels as oral devices for modified release of drugs was studied. For this, a kinetic model of solute release was elaborated whose results served as parameters for evaluation of such application. In that model the solute release is dependent of the diffusion properties and its partition on solution-hydrogel phases. The model predicts the whole profile of solute release no important the geometric form of hydrogel. The potential uses of these smart hydrogels as oral devices for potassium diclofenac release was evaluated based in the parameters from the mathematical model, like release rate constant, kR, and half life time for releasing, tl/2. These results demonstrated that the hydrogels of AGm cross-linked in the presence of the DMAAm and acid MetAc monomers presented potentials to be used as oral devices for modified release of drugs.