Advanced cardiovascular stent coated with nanofiber.
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 presence of 600 μM H2O2, and from 86.8 ± 8.4% to 59.4 ± 8.7% in the presence of 1.0 mM H2O2, suggesting that β-estradiol efficiently protected hPCECs from ROS induced cytotoxicity. The level of NO production in hPCECs in the presence of β-estradiol after 6 days of incubation was much greater than that of the control without β-estradiol. In summary, nanofibers loaded with nanoparticles containing β-estradiol could be used as a suitable platform for the surface coating of a cardiovascular stent, achieving enhanced endothelialization at the implanted sites of blood vessels.
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City , Kansas City, Missouri 64108, United States.
Byeongtaek
B
Oh
Chi H
CH
Lee
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D023903:Coronary Restenosis / Q000517:prevention & control*; D004337:Drug Carriers / Q000737:chemistry; D054855:Drug-Eluting Stents; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D057139:Nanofibers / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D020005:Propanols / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated
D048271:Chitosan; D004337:Drug Carriers; D004958:Estradiol; D006861:Hydrogen Peroxide; D019344:Lactic Acid; D009569:Nitric Oxide; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011109:Polymethacrylic Acids; D020005:Propanols; D017382:Reactive Oxygen Species; C038300:methylmethacrylate-methacrylic acid copolymer; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated