D. Teomim et al., Perivascular delivery of heparin for the reduction of smooth muscle cell proliferation after endothelial injury, J CONTR REL, 60(1), 1999, pp. 129-142
Thin flexible sheets composed of poly(lactic acid) (PLA) laminated polyanhy
dride, poly(erucic acid dimer-sebacic anhydride) (P(EAD-SA)), loaded with h
eparin were evaluated in vitro and in vivo. PLA was used for coating the po
lyanhydride to improve the release profile and improve the strength of the
films. Heparin was released constantly for 20 days from PLA-coated 2% loade
d P(EAD-SA). The uncoated film of P(EAD-SA) released heparin for only 4 day
s. The localized delivery of heparin around the carotid artery was investig
ated by implanting polymer loaded with [H-3]heparin around the carotid arte
ry of rats and the heparin release and tissue distribution was monitored. T
he maximum heparin concentration in the artery exposed to the drug was on d
ay 4 for the P(EAD-SA) uncoated device (fast releasing system) and day 11 f
or the coated devices. The control artery, the uncovered segments of the ar
tery, and the surrounding tissue contained negligible amounts of radioactiv
ity. These data confirm that heparin was delivered locally without systemic
exposure. Two independent animal studies were conducted to evaluate the ef
fectiveness of these heparin-releasing devices. In both studies the balloon
catheter injury in a rat model was used. After inflicting an injury to the
common carotid, a matrix oriented with its long axis along the artery was
placed under the injured portion of the vessel. In both studies the treated
rats showed a very thin layer of neointima where the control group showed
a significant reduction of the artery internal diameter with SMC neointima
ratio greater than 1. (C) 1999 Elsevier Science B.V. All rights reserved.