Advanced Cardiovascular Stent Coated with Nanofiber

• Published in: Molecular pharmaceutics 2013-12, Vol.10 (12), p.4432-4442
• Main Authors: Oh, Byeongtaek, Lee, Chi H
• Format: Article
• Language: English
• Subjects: Cell Proliferation - drug effects; Cells, Cultured; Chemistry, Pharmaceutical - methods; Chitosan - chemistry; Coronary Restenosis - prevention & control; Drug Carriers - chemistry; Drug-Eluting Stents; Estradiol - chemistry; Estradiol - pharmacology; Humans; Hydrogen Peroxide - chemistry; Lactic Acid - chemistry; Nanofibers - chemistry; Nanoparticles - chemistry; Nitric Oxide - metabolism; Polyglycolic Acid - chemistry; Polymers - chemistry; Polymethacrylic Acids - chemistry; Propanols - chemistry; Reactive Oxygen Species - metabolism
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp400231p

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 β-estradiol. 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-fold greater than the control (without β-estradiol). The cells treated with the enhanced level of H2O2 (>1 mM: as ROS source) were mostly nonviable (81.1 ± 12.4%, p < 0.01), indicating that ROS induce cell apoptosis and trigger the rupture of atheroma thin layer in a concentration dependent manner. Nanofibers containing β-estradiol (0.5 mM) lowered cellular cytotoxicity from 25.2 ± 4.9% to 8.1 ± 1.4% in the