科研之友
微信
新浪微博
Facebook
分享链接
摘要
Nanofiber was explored as a stent surface coating substance for the treatment of coronary artery diseases (CAD). Nanofibers loaded with nanopartides containing beta-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. beta-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 nanopartides (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 beta-estradiol, the release profiles of beta-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 mu g respectively. The nanofibers of NP-CHB coated on metallic mandrel offered the most sustained release profile of beta-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 beta-estradiol yielded a high endothelial proliferation rate, which was about 3-fold greater than the control (without beta-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 beta-estradiol (0.5 mM) lowered cellular cytotoxicity from 25.2 +/- 4.9% to 8.1 +/- 1.4% in the presence of 600 mu M H2O2, and from 86.8 +/- 8.4% to 59.4 +/- 8.7% in the presence of 1.0 mM H2O2, suggesting that beta-estradiol efficiently protected hPCECs from ROS induced cytotoxicity. The level of NO production in hPCECs in the presence of beta-estradiol after 6 days of incubation was much greater than that of the control without beta-estradiol. In summary, nanofibers loaded with nanopartides containing beta-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.
- 出版日期2013-12
