Développement de systèmes bio-polymériques pour la délivrance de molécules d'intérêt biologique

The March 20, 2012

Directeurs de thèse : Messieurs Guillermo Raul CASTRO et Frank BOURY

Development of controlled release systems allows to improve drug administration in treatments of acute and/or chronic diseases. Congo Red (CR) dye was selected as a molecular aromatic drug model. Studies of the interaction of 9 biopolymers with CR model were performed. Alginate and Guar gum were selected and their coacervates were studied. Derivative carboxymethyl guar gum (CMGG) was synthesized and characterized, in order to improve aqueous solubility. The systems were analyzed by FTIR spectroscopy, elemental analysis, surface tension and rheological measurements. Best encapsulation of Congo red was obtained in alginate and CMGG coacervate microspheres. Vibrational spectroscopies revealed interaction among CR and the biopolymer matrix attributed to the aromatic motif of the dye with apolar regions of alginate. Controlled release of CR was pH dependant. Studies of biopol-Doxorubicin (Dox) interactions were then carried out, to select the best matrix. Pectins and carragenines showed the highest interactions with the drug. Kinetic Dox release showed 80.0 and 15.0 % free drug from 35 and 55 % Pec formulations. FTIR analysis of Pec-Dox complex showed hipsochromic effects suggesting strong interaction between the drug cargo and the matrix. Rheological studies of Pec and Pec-dox samples flow behavior exhibited a shear-thinning nature, and confirmed those significant interactions. This formulation was considered for the development of an hybrid biopolymeric-inorganic systems to reduce the particles size and to control their porosity in order to manipulate the Dox release profile in alkaline conditions. Syntheses of hybrid particles of CaCO3 (MPh) in presence of pectins and carragenines were developed by supercritical fluids and chemical process. The biomolecules worked like templates allowing the crystallization the vaterite polymorph with a purity higher than 95 %. The MPh presented a Dox load bigger than 90%, a very promising result for future biomedical applications.