In vitro and in vivo evaluation of pectin beads for the colon delivery of β-lactamases

Abstract

The aim of the present study was to provide a “proof of concept” of colon delivery of β-lactamases by pectin beads aiming to degrade residual β-lactam antibiotics, in order to prevent the emergence of resistant bacterial strains.

Pectin beads were prepared according to ionotropic gelation method using CaCl₂ as a gelling agent. Particles were then washed and soaked in polyethylenimine (PEI). Coating beads with PEI considerably improved their stability in simulated intestinal medium. In vitro studies showed that β-lactamases were released from pectin beads in colonic medium due to the action of pectinolytic enzymes. When ampicillin was added to this medium, the release of β-lactamases induced, as expected, the antibiotic inactivation. Finally, after oral administration of loaded-beads to CD1 mice, β-lactamases were retrieved in high concentrations in faeces. Observation by SEM of beads extracted from mice intestinal tracts concluded the core degradation of beads without any modification of the PEI coating layer.

This study demonstrates that a multiparticulate system with suitable characteristics for site-specific colonic delivery can be prepared. This system could be used to target β-lactamases to the colon in order to hydrolyse antibiotic residues during treatment and prevent their impact on colonic microflora.

Keywords: :

• Pectin beads
• β lactamase
• colon delivery
• β lactams
• antibiotic resistances