Colonic delivery of β-lactamases does not affect amoxicillin pharmacokinetics in rats

Abstract

Pectin beads containing β-lactamases were designed for the hydrolysis of colonic residual antibiotics responsible for the emergence of resistance. Beads were prepared by ionotropic gelation in CaCl₂ and stabilized by coating with polyethylenimine (PEI) to resist disintegration in the upper GI tract. Particle characterization showed that dried beads had a diameter around 1 mm independently of the presence of PEI. Seven to ten percent (w/w) of PEI was located on bead surface forming a coating layer as observed by scanning electron microscopy. PEI improved considerably bead stability in simulated intestinal medium while affecting slightly the encapsulation efficiency of active β-lactamases. Coated beads were able to preserve β-lactamases from premature leakage in the upper GIT whereas, in simulated colonic medium, pectinases induced matrix degradation and reduction of β-lactamase content especially in beads coated in a 0.8% PEI solution. Finally, the pharmacokinetics of amoxicillin in rat after oral administration was not modified by the co-administration of beads containing β-lactamases. In conclusion, PEI-coated beads are stable in the upper GIT but remain sensitive to the action of pectinolytic enzymes allowing release of β-lactamases in a colonic medium without modification of the absorption of a β-lactam antibiotic when co-administered with loaded beads. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 1853–1863, 2008