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Titolo:
Sustained release of heparin from polymeric particles for inhibition of human vascular smooth muscle cell proliferation
Autore:
Yang, ZH; Birkenhauer, P; Julmy, F; Chickering, D; Ranieri, JP; Merkle, HP; Luscher, TF; Gander, B;
Indirizzi:
Swiss Fed Inst Technol Zurich ETH, Dept Pharm, CH-8057 Zurich, SwitzerlandSwiss Fed Inst Technol Zurich ETH Zurich Switzerland CH-8057 Switzerland Univ Zurich Irchel, Inst Physiol, CH-8057 Zurich, Switzerland Univ Zurich Irchel Zurich Switzerland CH-8057 H-8057 Zurich, Switzerland Inselspital Bern, CH-3010 Bern, Switzerland Inselspital Bern Bern Switzerland CH-3010 ern, CH-3010 Bern, Switzerland Univ Zurich Hosp, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland Sulzer Innotec Carbomed, Austin, TX 78752 USA Sulzer Innotec Carbomed Austin TX USA 78752 arbomed, Austin, TX 78752 USA
Titolo Testata:
JOURNAL OF CONTROLLED RELEASE
fascicolo: 2-3, volume: 60, anno: 1999,
pagine: 269 - 277
SICI:
0168-3659(19990805)60:2-3<269:SROHFP>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
KINASE-C-ALPHA; TRANSLUMINAL CORONARY ANGIOPLASTY; DRUG-DELIVERY; GROWTH-FACTOR; BALLOON ANGIOPLASTY; DOUBLE-BLIND; IN-VITRO; RESTENOSIS; INJURY; GRAFT;
Keywords:
heparin release; PLGA microspheres; human smooth muscle cell (SMC) culture; PDGF; saphenous vein;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Gander, B Swiss Fed Inst Technol Zurich ETH, Dept Pharm, Wintherthurerstr 190, CH-8057 Zurich, Switzerland Swiss Fed Inst Technol Zurich ETH Wintherthurerstr 190 Zurich Switzerland CH-8057
Citazione:
Z.H. Yang et al., "Sustained release of heparin from polymeric particles for inhibition of human vascular smooth muscle cell proliferation", J CONTR REL, 60(2-3), 1999, pp. 269-277

Abstract

Vascular smooth muscle cell (SMC) growth plays an important role in atherosclerosis, restenosis and venous bypass graft disease. With systemic drug administration no effective therapy for restenosis and venous bypass graft disease is available. This could be due to low local concentrations of the drugs at the target site. A directed delivery of drugs to tissues with a sustained release system during pel cutaneous transluminal coronary angioplasty (PTCA) or during bypass surgery could provide high concentrations of drugs at the target site and avoid systemic side effects. In the present study heparin was encapsulated by spray-drying into biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) to obtain a system for prolonged drug release. SMC were cultured from saphenous vein explants obtained from patients undergoing coronary bypass surgery. Cell proliferation was measured by [H-3]thymidine incorporation. Heparin release from PLGA 50:50 microspheres in an isoosmolar PBS buffer (pH=7.4) showed a triphasic profile with an initial burst (completed after 24 h), a dormant period and a final stage with increased release rate, which lasted about 10-14 days. Cell proliferation as measured by [H-3]thymidine incorporation was markedly stimulated by platelet-derivedgrowth factor-BE (PDGF-BB) (5 ng/ml) or serum (5%). Proliferation of SMC was equally reduced (50% P<0.05; n=9-11) by native heparin or heparin released from PLGA microspheres, while PLGA microspheres without heparin loading had no effect on [3H]thymidine incorporation in human SMC. Similar results were also obtained when SMC were stimulated with 5% serum instead of PDGF-BB (50%; P<0.05; n=6). Thus, heparin encapsulated into PLGA microspheres wasreleased over a prolonged period of time and thereby effectively reduced human SMC proliferation stimulated either with PDGF or serum. Biodegradable PLGA microspheres may also be used to encapsulate other antiproliferative agents and provide a new approach for local drug delivery after PTCA. This may help to prevent restenosis after PTCA or to reduce graft disease after coronary bypass graft surgery. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 20:49:47