Journal
BIOMATERIALS
Volume 28, Issue 28, Pages 4124-4131Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2007.05.034
Keywords
PTH; Pulsatile release; controlled drug delivery; osteoporosis; polyanhydride; bone tissue engineering
Funding
- NIDCR NIH HHS [R01 DE015384-04, R01 DE017689, DE017689, R01 DE015384-03, R01 DE015384, DE015384, R01 DE017689-01A1] Funding Source: Medline
- NIDDK NIH HHS [DK053904, R01 DK053904-08, R01 DK053904, R01 DK053904-09] Funding Source: Medline
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Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(L-lactic acid) (PLLA), using a reverse solid-free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(p-carboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies. (c) 2007 Elsevier Ltd. All rights reserved.
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