POLYSACCHARIDE BEADS FOR COLON DELIVERY OF ANTIBIOTIC DEGRADING ENZYMES

It is now recognized that the increased resistance of bacterial pathogens is in most instances related to an increased resistance in commensal intestinal flora followed by horizontal transfer of resistance to pathogenic species. The presence of residual antibiotics in the colon leads to a disruption of the colonic microflora and consequently to the reduction of colonization resistance (1). Therefore, the colonic delivery of antibiotic -degrading enzymes might protect colonic microflora and help to fight against the spreading of resistant bacterial strains in the environment due to intensive use of antibiotics. Particles for the colon delivery of β-lactamases (BL) have been designed for degradation of residual βlactams and to minimise resistance to this class of antibiotics. Bacterially-triggered delivery systems display great potentialities for site specific targeting of peptides and proteins to the colon. In this case, drug delivery can be achieved by exploiting microbial enzyme activity predominantly present in that location (2). Pectin, a naturally occurring polysaccharide found in plant cell walls, has been used as the main component of colonic drug delivery systems. Pectin is composed of linear chains of α(1-4)-D-galacturonic acid residues whose carboxylic groups are partially methoxylated. Some of the carboxylic groups may also be converted to carboxamide, producing amidated pectin. In addition, pectin is non toxic, not digested by gastric or intestinal enzymes and almost totally degraded by pectinolytic enzymes produced by the colonic microflora. The mild conditions of encapsulation using ionotropic gelation in calcium should be ideal to entrap sensitive molecules such as BL. The presentation will focus on the development of pectin particles for the colon delivery of BL and subsequent degradation of residual antibiotics.