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Advanced Cardiovascular Stent coated with Nanofiber Byeongtaek Oh, and Chi H. Lee Mol. Pharmaceutics, Just Accepted Manuscript • DOI: 10.1021/mp400231p • Publication Date (Web): 19 Sep 2013 Downloaded from http://pubs.acs.org on September 26, 2013
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Molecular Pharmaceutics
Title: Advanced Cardiovascular Stent coated with Nanofiber Authors: Byeongtaek Oh 1 and Chi H. Lee 1,* 1 Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO 64108, USA
*Correspondent Author
Chi H. Lee, Ph.D. Professor 2464 Charlotte Street, HSB-4242 Division of Pharmaceutical Sciences University of Missouri at Kansas City Kansas City, MO 64108 816-235 2408 (Tel) 816-235-5779 (Fax)
[email protected] 1 ACS Paragon Plus Environment
Molecular Pharmaceutics
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Table of Content/Abstract graphic
2 ACS Paragon Plus Environment
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Molecular Pharmaceutics
ABSTRACT Nanofiber was explored as a stent surface coating substance for the treatment of coronary artery diseases (CAD). Nanofibers loaded with nanoparticles containing β-Estradiol were developed and exploited to prevent stent-induced restenosis through regulation of the reactive oxygen species (ROS). Eudragit S-100 (ES), a versatile polymer, was used as a nanoparticle (NP) base, and the mixtures of Hexafluoro-2-propanol (HFIP), PLGA and PLA at varying ratios were used as a nanofiber base. β-Estradiol was used as a primary compound to alleviate the ROS activity at the subcellular level. Nile-Red was used as a visual marker. Stent was coated with nanofibers produced by electrospinning technique comprising the two-step process. Eudragit-Nanoparticles (ES-NP) as well as 4 modified types of NP-W (ES-NP were dispersed in H2O, which was mixed with HFIP (1:1 (v/v) and then subsequently added with 15% PLGA), NP-HW (ES-NP were dispersed in H2O, which was mixed with HFIP (1:1 (v/v)) already containing 15% PLGA), NP-CHA (ES-NP with a Chitosan layer were added in H2O, which was mixed with HFIP (1:1 (v/v)) containing 15% PLGA), and NP-CHB (ES-NP with a Chitosan layer were added in H2O, which was mixed with HFIP (1:1 (v/v)) containing the mixture of PLGA and PLA at a ratio of 4:1), were developed and their properties, such as the loading capacity of β-Estradiol, the release profiles of β-Estradiol, cell cytotoxicity and antioxidant responses to ROS, were characterized and compared. Among composite nanofibers loaded with nanoparticles, NP-CHB had the maximal yield and drug-loading amount of 66.5±3.7 % and 147.9±10.1 µg, respectively. The nanofibers of NP-CHB coated on metallic mandrel offered the most sustained release profile of βEstradiol. In the confocal microscopy study, NP-W exhibited a low fluorescent intensity of Nile-Red as compared with NP-HW, indicating that the stability of nanoparticles decreased, as the percentage volume of the organic solvent increased. Nanofibers incorporated with β-Estradiol yielded a high endothelial proliferation rate, which was about 3 folds greater than the control (without β-Estradiol). The cells treated with the enhanced level of H2O2 (> 1mM: as ROS source) were mostly non-viable (81.1±12.4%, p
