Biopolymer-based hybrid hydrogels for biomedical applicationsfrom macroscopic to nanosized systems

Abstract

Biopolymer-based carrier particles are biocompatible and offer the ability to incorporate hydrophilic and hydrophobic active agents. The incorporation of a drug into a polymeric matrix can enhance its protection against degradation in harsh physiological media. In addition, it can control the release to the specific site of action, with increased therapeutic bioavailability and minimized side effects or toxicity. This thesis presents the preparation of different polysaccharide hybrid systems for encapsulating hydrophilic substances, which are subsequently released. Carriers ranging from macroscopic to nanometric size are produced by different methods: ionotropic gelation, spray drying, and nanoemulsion techniques. Chitosan and alginate are used as matrix polymers and silica is applied as a structuring additive. In the first part of the work, an organic–inorganic macroscopic gel is prepared by a simple process involving ionotropic gelation, and the efficiency of the method for entrapping hydrophilic molecules (erioglaucine disodium salt and ephedrine hydrochloride) is investigated. The release of the encapsulated substances is controlled by tailoring the hybrid network structure. The second approach involves the preparation of microcapsules by using ionotropic gelation followed by spray drying. In this process, which is fast and continuous, a liquid feed is transformed into dry particles. The release behavior of hydrophilic drugs is studied and compared with the results obtained in the first part for macroscopic particles. In addition, the biopolymer microparticles are loaded with Pd(II) ions and, after reduction to Pd(0), applied as catalysts for a model reaction, namely the reduction of 4 nitrophenol by sodium borohydride. The third approach consists in the preparation of an organic–inorganic nanogel by two different inverse nanoemulsion methods. The first method is a “one-nanoemulsion” process in which chitosan nanoparticles are produced by allowing the diffusion of a cross-linking agent to a nanoemulsion containing a solution of chitosan in the dispersed phase. In the second method, a polysaccharide nanoemulsion is mixed with a second cross-linking nanoemulsion. A nanogel is formed after fusion of the droplets of the two nanoemulsions. In the systems prepared by the three approaches, silica nanostructures are homogeneously incorporated within the polymer matrix. The release behavior depends on the preparation method, the size of the structures, and the presence or not of silica. Overall, it can be concluded that silica plays a very important role in both increasing the structural stability of the hydrogel carriers and retarding the release in different media.