Date of Award

1-1-2012

Document Type

Campus Access Thesis

Department

Biomedical Science

First Advisor

Kevin CARNEVALE

Abstract

The development ofdrug eluding stents (DES) have prolonged the progression of restenosis in coronary arteries, however, their use in larger vessels remain suboptimal. The drugs elude off within the first week, and a delayed release may retard development of restenosis in larger vessels. Therefore, biodegradable core-shell polymeric nanoparticle (NP), with a hydrophobic core and hydrophilic shell was developed for surfactant-free encapsulation and delivery of Everolimus from DES. Elution of Everolimus was measured from Poly (lactide-fumarate)(PLAF) and Poly (lactide-co-ethylene oxide fumarate))(PLEOF) nanoparticle. Synthesis of the 90%PLAF/10%PLEOF NPs and characterization with respect to particle size distribution, morphology, and loading efficiency and the elution of Everolimus loaded nanoparticle under coated conditions were investigated. PLEOF macromer, due to its amphiphilic nature, acted as a surface active agent in the process ofself-assembly which produced core-shell NPs with PLAF and PLEOF macromers as the core and shell. The encapsulation efficiency ranged from 90% to 96% at concentrations from 6% to 15% of Everolimus, respectively, and it was independent of the macromer and increased with increasing concentration of Everolimus. Most of the PLAF NP degraded in 30 days which demonstrated that the release was dominated by hydrolytic degradation and erosion of the matrix. The percent release from polyurethane coating was reduced with the 12% Everolimus (6mg) PLAF/PLEOF NPs to 48% from 64% of the same concentration of Everolimus alone after 30 days. These results show that usingbiodegradable PLAF/PLEO NPs can reduce the elution of Everolimus from coated condition and may extend the ability to reduce restenosis in drug eluding stents.

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