Journal article
Controlled-Release Drug Delivery of Diphosphonates to Inhibit Bioprosthetic Heart Valve Calcification: Release Rate Modulation with Silicone Matrices Via Drug Solubility and Membrane Coating
Journal of pharmaceutical sciences, v 76(4)
Apr 1987
PMID: 3110404
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Calcification (CALC) is the most frequent cause of the clinical failure of bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. The present investigation describes the formulation, characterization, and the in vivo efficacy of prolonged controlled-release silicone matrices containing the anticalcification agent disodium 1,1-hydroxyethylidene diphosphonate (Na2EHDP). Controlled release of EHDP was regulated by codispersions of Na2EHDP and the less soluble salt Ca2EHDP. Prolonged and constant release rates (zero-order) were obtained by coating silicone matrices with permeable silicone membranes, which were prepared by leaching with acetone pre-embedded polyethyleneglycol. All EHDP-containing matrices (co-implanted subdermally with BHV cusps in rats) significantly inhibited BHV CALC without detectable adverse effects on bone mineral and calcium metabolism. Matrices containing Na2EHDP:Ca2EHDP ratios of 10:90 or greater with respect to Na2EHDP completely inhibited CALC. Significant inhibition of BHV CALC was also observed with prereleased matrices (5months in vitro), thus demonstrating prolonged efficacy. It is concluded that sustained release of effective anticalcification therapy without side effects was achieved by using codispersions of calcium and sodium EHDP salts, and that a delayed and/or constant release rate of EHDP was obtained by coating reservoir-type matrices with silicone membranes that were pre-embedded with polyethyleneglycol.
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Details
- Title
- Controlled-Release Drug Delivery of Diphosphonates to Inhibit Bioprosthetic Heart Valve Calcification: Release Rate Modulation with Silicone Matrices Via Drug Solubility and Membrane Coating
- Creators
- Gershon Golomb - Hebrew University of JerusalemMark Dixon - Johns Hopkins HospitalMary Sue Smith - Drexel UniversityFrederick J. Schoen - Brigham and Women's HospitalRobert J. Levy - C. S. Mott Children's HospitalMichael John Dixon - Digital Media
- Publication Details
- Journal of pharmaceutical sciences, v 76(4)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Digital Media
- Web of Science ID
- WOS:A1987H387400001
- Scopus ID
- 2-s2.0-0023227630
- Other Identifier
- 991019184291104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal
- Chemistry, Multidisciplinary
- Pharmacology & Pharmacy