title: Influence of cross-linking agent type and chitosan content on the performance of pectinate-chitosan beads aimed for colon-specific drug delivery.
abstract: Pectinate-chitosan-beads aimed for colon theophylline delivery have been developed. The effect of zinc or calcium ions as cross-linking agent, and of chitosan concentration on the properties and colon-targeting performance of beads was investigated. Beads were characterized for morphology, entrapment efficiency and mucoadhesion properties. Zn-pectinate-chitosan beads formed a stronger gel network than the Ca-containing ones, enabling a greater entrapment efficiency, which further increased with chitosan content, probably due to polyelectrolyte complexes formation. Transport studies across Caco-2 cells evidenced a significant (p > 0.05) drug permeation increase from all beads with respect to drug alone, attributable to the enhancer and/or mucoadhesion properties of the polymers, and Ca-pectinate-chitosan beads were more effective than the Zn-containing ones. Beads formulated as enteric-coated tablets demonstrated good colon-targeting properties, and no differences were observed in drug-release profiles from Zn- or Ca-pectinate-chitosan beads. Therefore, Ca-pectinate-chitosan beads emerged as the choice formulation, joining colon-targeting specificity with better permeation enhancer power.
authors.affiliation: Department of Pharmaceutical Sciences, University of Florence, 50019 Florence, Italy. francesca.maestrelli@unifi.it
authors.forename: F
authors.initials: F
authors.lastname: Maestrelli
authors.forename: M
authors.initials: M
authors.lastname: Cirri
authors.forename: N
authors.initials: N
authors.lastname: Mennini
authors.forename: M
authors.initials: M
authors.lastname: Bragagni
authors.forename: N
authors.initials: N
authors.lastname: Zerrouk
authors.forename: P
authors.initials: P
authors.lastname: Mura
mesh_terms: D000268:Adhesiveness; D018938:Caco-2 Cells; D002118:Calcium / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D003106:Colon / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008863:Microspheres; D010368:Pectins / Q000737:chemistry*; D012995:Solubility; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D005079:Excipients; D005765:Gastrointestinal Agents; D010368:Pectins; D048271:Chitosan; D013806:Theophylline; D015032:Zinc; D002118:Calcium