Pulsatile release of parathyroid hormone from an implantable delivery system.
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.
Liu
Xiaohua
X
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Pettway
Glenda J
GJ
McCauley
Laurie K
LK
Ma
Peter X
PX
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D003652:Decanoic Acids / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004343:Drug Implants; D006801:Humans; D062425:Hydroxybenzoate Ethers; D062385:Hydroxybenzoates / Q000737:chemistry / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013499:Surface Properties; D019379:Teriparatide / Q000378:metabolism*
D001672:Biocompatible Materials; D003652:Decanoic Acids; D003692:Delayed-Action Preparations; D003998:Dicarboxylic Acids; D004337:Drug Carriers; D004343:Drug Implants; D062425:Hydroxybenzoate Ethers; D062385:Hydroxybenzoates; D011108:Polymers; D019379:Teriparatide; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; C078320:1,3-bis(4-carboxyphenoxy)propane; D011092:Polyethylene Glycols; C011107:sebacic acid