Fabrication of an alpha-lipoic acid-eluting poly-(D,L-lactide-co-caprolactone) cuff for the inhibition of neointimal formation.
The purpose of this study was to develop a novel polymer cuff for the local delivery of alpha-lipoic acid (ALA) to inhibit neointimal formation in vivo. The polymer cuff was fabricated by incorporating the ALA into poly- (D,L-lactide-co-caprolactone) 40:60 (PLC), with or without methoxy polyethylene glycol (MethoxyPEG). The release kinetics of ALA and in vitro degradation by hydrolysis were analyzed by HPLC and field emission scanning electron microscopy (FE-SEM), respectively. In vivo evaluation of the effect of the ALA-containing polymer cuff was carried out using a rat femoral artery cuff injury model. At 24 h, 48% or 87% of the ALA was released from PCL cuffs with or without MethoxyPEG. FE-SEM results indicated that ALA was blended homogenously in the PLC with MethoxyPEG, whereas ALA was distributed on the surface of the PLC cuff without MethoxyPEG. The PLC cuff with MethoxyPEG showed prolonged and controlled release of ALA in PBS, in contrast to the PLC cuff without MethoxyPEG. Both ALA-containing polymer cuffs had a significant effect on the inhibition of neointimal formation in rat femoral artery. Novel ALA-containing polymer cuffs made of PLC were found to be biocompatible and effective in inhibiting neointimal formation in vivo. Polymer cuffs containing MethoxyPEG allowed the release of ALA for one additional week, and the rate of drug release from the PLC could be controlled by changing the composition of the polymer. These findings demonstrate that polymer cuffs may be an easy tool for the evaluation of anti-restenotic agents in animal models.
Lee
Hyo Jeong
HJ
Department of Internal Medicine and Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, 700-721, Korea.
Choi
Seung Hee
SH
Nah
Mun Hee
MH
Lim
Jeong Ok
JO
Lee
In Kyu
IK
D000818:Animals; D023903:Coronary Restenosis / Q000628:therapy*; D003692:Delayed-Action Preparations; D008297:Male; D008422:Materials Testing; D011091:Polyesters / Q000008:administration & dosage* / Q000138:chemical synthesis*; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
D003692:Delayed-Action Preparations; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; C062968:lactide-caprolactone copolymer