title: Time-programmed pulsatile release of dextran from calcium-alginate gel beads coated with carboxy-n-propylacrylamide copolymers.
abstract: Time-programmed release of macromolecular drugs was achieved by utilization of calcium-alginate gel beads modified with coated copolymer layers. Modified calcium-alginate gel beads coated with poly(carboxy-n-propylacrylamide-co-dimethylacrylamide) [poly(CNPAAm-co-DMAAm)] (22.7 mol% of CNPAAm) of varying coating thickness from 25 to 125 microm were developed as drug carriers. Model macromolecular drugs used were fluorescein isothiocyanate (FITC)-labeled dextrans with different molecular weights ranging from 9400 to 145000. FITC-dextran release was strongly dependent on both copolymer coating thicknesses and the dextran molecular weights. Release of FITC-dextran (MW 9400) followed Fickian diffusion according to t(1/2) dependence, indicating that the drug diffusion is the main driving force for release of dextran MW 9400. Release of higher molecular weight FITC-dextrans (71,00 and 145,00) exhibited a burst-effect preceded by a preset lag time. These release profiles were governed by the dissociation of calcium ions from polyguluronate sequences in alginate molecules along with the diffusion of sodium ions into the gel bead core. This created osmotic pressure inside the gel, inducing breakage of the coated copolymer layer and accelerated drug release. Burst release of macromolecular drugs thus occurred after a certain lag period. The lag time was regulated by the copolymer coat thickness. A pulsatile release of FITC-dextran was demonstrated by combining a series of modified alginate gel beads in a single batch.
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawadacho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: Rinat M
authors.initials: RM
authors.lastname: Iskakov
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
mesh_terms: D000180:Acrylic Resins / Q000493:pharmacokinetics*; D000464:Alginates / Q000493:pharmacokinetics*; D000925:Anticoagulants / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D003911:Dextrans / Q000493:pharmacokinetics*; D005782:Gels / Q000493:pharmacokinetics*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D011108:Polymers / Q000493:pharmacokinetics; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000464:Alginates; D000925:Anticoagulants; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D003911:Dextrans; D005782:Gels; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D011108:Polymers; D000099166:Polyacrylamides