Nitric oxide-generating hydrogels inhibit neointima formation.
This study evaluated the effects of localized delivery of nitric oxide (NO) from hydrogels covalently modified with S-nitrosocysteine (Cys-NO) on neoinitma formation, a key component of restenosis, in a rat balloon-injury model. Soluble Cys-NO was used in preliminary studies to identify dosage ranges that were able to simultaneously inhibit smooth muscle cell proliferation, enhance endothelial cell proliferation, and reduce platelet adhesion. Photo-cross-linked PEG-based hydrogels were formed with covalently immobilized Cys-NO. These materials release NO for approximately 24 h and can be applied to tissues and photo-cross-linked in situ to form local drug-delivery systems. Localized delivery of NO from hydrogels containing Cys-NO inhibited neointima formation in a rat balloon-injury model by approximately 75% at 14 days.
Department of Chemical Engineering, Rice University, Houston, TX 77005-1892, USA.
Kristyn S Bohl
KS
Masters
Elizabeth A
EA
Lipke
Elizabeth E H
EE
Rice
Meghan S
MS
Liel
Heather A
HA
Myler
Corinna
C
Zygourakis
David A
DA
Tulis
Jennifer L
JL
West
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D020100:Hydrogels; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols / Q000008:administration & dosage / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects* / Q000502:physiology
D020100:Hydrogels; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D006152:Cyclic GMP; D003545:Cysteine