Yao Guang-Tao, Song Li-Ping, Xue Wan-Hua, Su Guo-Hai, Ning Ai-Hua, Wang Jin
Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013 Shandong, China.
Department of Cardiology, Dezhou People's Hospital, Dezhou, 253014 Shandong, China.
Saudi J Biol Sci. 2018 Sep;25(6):1016-1021. doi: 10.1016/j.sjbs.2017.03.015. Epub 2017 Apr 4.
Atorvastatin (ATV) may support mesenchymal stem cells (MSC) survival in post-infarct myocardium (MI) as inflammatory reactions, oxidative stress and hypoxia condition get started in such tissues after damage. However, limited aqueous insolubility and rapid first-pass metabolism reduce the systemic availability of ATV. The aim of the present investigation was to develop ATV loaded nanoparticles (ATVNPs) which might ensure the maximum availability of ATV in systemic circulation for longer duration and to strengthen the support to MSC survival. ATVNPs were synthesized using double emulsion solvent evaporation method and characterized as spherical shape, positive charged, nanoparticles of uniform size distribution and higher entrapment efficiency. ATVNPs were non-cytotoxic and showed sustained release (up to 28 days). Assessment of cardiac function (in terms of echocardiographic and left heart catheterization parameters) and cytokines estimation revealed efficient improvement in post-infarct myocardium condition of rat. In conclusion, ATVNP was developed successfully that may ensure safe, cost effective, and efficacious treatment of post-infarct myo-cardium when compared with that of MSC alone and MSC supplemented with ATV solution.
阿托伐他汀(ATV)可能有助于梗死心肌(MI)中骨髓间充质干细胞(MSC)的存活,因为损伤后此类组织中会引发炎症反应、氧化应激和缺氧状况。然而,有限的水不溶性和快速的首过代谢降低了ATV的全身可用性。本研究的目的是开发负载阿托伐他汀的纳米颗粒(ATVNPs),以确保ATV在体循环中更长时间的最大可用性,并加强对MSC存活的支持。采用复乳溶剂蒸发法合成了ATVNPs,其特征为球形、带正电荷、粒径分布均匀且包封率较高的纳米颗粒。ATVNPs无细胞毒性,并显示出持续释放(长达28天)。心脏功能评估(根据超声心动图和左心导管插入术参数)和细胞因子测定显示,大鼠梗死心肌状况有有效改善。总之,与单独使用MSC以及使用ATV溶液补充的MSC相比,成功开发的ATVNP可确保对梗死心肌进行安全、经济有效且有效的治疗。