Perivascular graft heparin delivery using biodegradable polymer wraps

Citation
Er. Edelman et al., Perivascular graft heparin delivery using biodegradable polymer wraps, BIOMATERIAL, 21(22), 2000, pp. 2279-2286
Citations number
40
Categorie Soggetti
Multidisciplinary
Journal title
BIOMATERIALS
ISSN journal
01429612 → ACNP
Volume
21
Issue
22
Year of publication
2000
Pages
2279 - 2286
Database
ISI
SICI code
0142-9612(200011)21:22<2279:PGHDUB>2.0.ZU;2-K
Abstract
Heparin remains the gold-standard inhibitor of the processes involved in th e vascular response to injury. Though this compound has profound and wide-r eaching effects on vascular cells in culture and animal models, its clinica l utility has been questionable at best. It is clear that the mode of hepar in delivery is critical to its potential and it may well be that routine fo rms of administration are insufficient to observe benefit given the heparin 's short half-life and complex pharmacokinetics. When ingested orally, hepa rin is degraded to inactive oligomer fragments while systemic administratio n is complicated by the need for continuous infusion and the potential for uncontrolled hemorrhage. Thus alternative heparin delivery systems have bee n proposed to maximize regional effects while limiting systemic toxicity. Y et, as heparin is such a potent antithrombotic compound and since existing local delivery systems lack the ability to precisely regulate release kinet ics, even site-specific therapy is prone to bleeding. We now describe the d esign and development of a novel biodegradable system for the perivascular delivery of heparin to the blood vessel wall with well-defined release kine tics. This system consists of heparin-encapsulated poly(DL lactide-co-glyco lide) (pLGA) microspheres sequestered in an alginate gel. Controlled releas e of heparin from this heterogeneous system could be obtained over a period of 25 days in vitro. The experimental variables affecting heparin release from these matrices were investigated. Gel permeation chromatography (GPC) and scanning electron microscopy (SEM) were used to monitor the degradation process and found to correlate well with the release kinetics. Heparin-rel easing gels inhibited growth of bovine vascular smooth muscle cells in tiss ue culture in a dose-dependent manner. Moreover, gel release controlled vas cular injury in denuding and interposition vascular graft animal models of disease even when uncontrolled bleeding was evident with standard matrix-ty pe release. This system may therefore provide an effective means of examini ng the effects of various compounds in the control of smooth muscle cell pr oliferation in accelerated arteriopathies and also shed light on the biolog ic nature of these processes. (C) 2000 Elsevier Science Ltd. All rights res erved.