Controlled release of bisphosphonate from a biodegradable implant: Evaluation of release kinetics and anticalcification effect

Gershon Golomb, Matilda Levi, Joel M. Van Gelder

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract The present investigation describes the formulation and the in vivo efficacy of prolonged controlled-release chitosan matrices, containing the novel anticalcification agents adipoyland suberoylbisphosphonate (AdBP and SuBP). Chitosan matrices were prepared by the solvent-cast method and the role of several factors such as polymer molecular weight (MW), crosslinking, and drug load concentration, on the release rate profile have been examined. Crosslinking of chitosan films retarded degradation rate of the polymer but not the release rate of the embedded drug. Chitosan's MW and drug load concentration did not affect drug release rate. The release kinetics of the bisacylphosphonates were characterized by initial burst-effect and pseudo zero-order kinetics in the following release phase. AdBP/chitosan matrices (co-implanted subdermally in rats with the calcifiable bioprosthetic heart valve tissue) significantly inhibited tissue calcification after 15 and 30 days implantation (66.4 and 108.6 ?g/mg Ca++ in comparison to 2.7 and 3.6 ?g/mg Ca++, untreated and treated groups, respectively). No side effects were noted.
Original languageAmerican English
Pages (from-to)23-28
Number of pages6
JournalJournal of Applied Biomaterials
Volume3
Issue number1
DOIs
StatePublished - 1992

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