Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia.
The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877-887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.
Kanjickal
Deenu
D
Department of Chemical Engineering, University of Akron, Akron, Ohio 44325, USA.
Lopina
Stephanie
S
Evancho-Chapman
Mary M
MM
Schmidt
Steven
S
Donovan
Duane
D
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D019245:Compressive Strength; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D001672:Biocompatible Materials; D007166:Immunosuppressive Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine