Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400 019, Maharashtra, India.
National Centre for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health, J. M. Street, Parel, Mumbai 400 012, Maharashtra, India.
Int J Pharm. 2021 May 1;600:120403. doi: 10.1016/j.ijpharm.2021.120403. Epub 2021 Mar 10.
Localized drug delivery with sustained elution characteristics from nanocarrier coated stents represents a viable therapeutic approach to circumvent concerns related to coronary stent therapy. We fabricated a Sirolimus (SRL) and Bivalirudin (BIV) releasing nanoparticles (NPs) coated stent for concurrent mitigation of vascular restenosis and acute stent thrombosis. SRL NPs were prepared by nanoprecipitation method whereas the BIV vesicles were generated using hydrophobic ion pair approach followed by micellization phenomenon. MTT assay and confocal microscopic analysis indicated superior anti-proliferative activity and higher cellular uptake of SRL NPs into human coronary artery smooth muscle cells, respectively. DSC and ATR-FTIR techniques confirmed the formation of complex between BIV and phosphatidylglycerol via some weak physical interactions. More than 2 fold rise in log P value was obtained for DSPG-BIV at 3:1 M ratio compared with native BIV solution. The SAXS analysis indicated formation of oligolamellar vesicles of DSPG-BIV complex which was preferentially entrapped into lipophilic lamellae of vesicles. APTT, PT, and TT tests revealed that the BIV vesicles caused significant prolongation of clotting time compared to native BIV solution. The SEM analysis showed uniform and defect free stent coating. In vitro release study demonstrated that SRL and BIV were eluted in a sustained manner from coated stents.
局部药物递送具有纳米载体涂层支架的持续洗脱特性，代表了一种可行的治疗方法，可以规避与冠状动脉支架治疗相关的问题。我们制备了一种同时减轻血管再狭窄和急性支架内血栓形成的西罗莫司（SRL）和比伐卢定（BIV）释放纳米颗粒（NPs）涂层支架。SRL NPs 通过纳米沉淀法制备，而 BIV 囊泡则通过疏水离子对方法生成，随后通过胶束化现象生成。MTT 测定和共聚焦显微镜分析分别表明 SRL NPs 具有更好的抗增殖活性和更高的细胞摄取率。DSC 和 ATR-FTIR 技术证实了 BIV 和磷脂酰甘油之间通过一些弱的物理相互作用形成复合物。与天然 BIV 溶液相比，在 3:1 M 摩尔比下，DSPG-BIV 的 log P 值增加了 2 倍以上。小角 X 射线散射（SAXS）分析表明形成了 DSPG-BIV 复合物的寡层囊泡，该复合物优先被包封在囊泡的亲脂性层中。APTT、PT 和 TT 测试表明，与天然 BIV 溶液相比，BIV 囊泡导致凝血时间显著延长。SEM 分析显示支架涂层均匀且无缺陷。体外释放研究表明，SRL 和 BIV 从涂层支架中以持续的方式洗脱。
