title: In vitro and in vivo evaluation of pectin beads for the colon delivery of beta-lactamases.
abstract: The aim of the present study was to provide a "proof of concept" of colon delivery of beta-lactamases by pectin beads aiming to degrade residual beta-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 beta-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 beta-lactamases induced, as expected, the antibiotic inactivation. Finally, after oral administration of loaded-beads to CD1 mice, beta-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 beta-lactamases to the colon in order to hydrolyse antibiotic residues during treatment and prevent their impact on colonic microflora.
authors.affiliation: University of Paris Sud, School of Pharmacy, UMR CNRS 8612, Group of targeting and delivery of poorly stable compounds, Châtenay-Malabry, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bourgeois
authors.forename: Antoun
authors.initials: A
authors.lastname: Laham
authors.forename: Madeleine
authors.initials: M
authors.lastname: Besnard
authors.forename: Antoine
authors.initials: A
authors.lastname: Andremont
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D003106:Colon / Q000187:drug effects* / Q000382:microbiology; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005243:Feces / Q000201:enzymology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010368:Pectins; D001618:beta-Lactamases / Q000008:administration & dosage* / Q000378:metabolism; D047090:beta-Lactams / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D047090:beta-Lactams; D010368:Pectins; D001618:beta-Lactamases