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Biodegradable stent coatings on the basis of PLGA polymers of different molecular mass, sustaining a steady release of the thrombolityc enzyme streptokinase
Reactive & Functional Polymers ( IF 5.1 ) Pub Date : 2020-03-09 , DOI: 10.1016/j.reactfunctpolym.2020.104550
M.A. Sevostyanov , A.S. Baikin , K.V. Sergienko , L.A. Shatova , A.A. Kirsankin , I.V. Baymler , A.V. Shkirin , S.V. Gudkov

The work describes synthesis of novel biodegradable polymer membranes based on poly(lactic-co-glycolic acid) (PLGA), as well as testing of their physicochemical properties. The membranes synthesized have been shown to possess the necessary mechanical properties and to be capable of sustained and directed release of large biomacromolecules, in particular, the molecules of streptokinase (m.w. 47 kDa). Streptokinase is a pharmaceutical drug with a high thrombolytic activity. The technology developed allows one to synthesize membranes with a relative elongation of 25 to 165% and a tensile strength of 20 to 55 MPa. The membranes are biodegradable; the rate of the polymer degradation in an isotonic solution is 0.5–1.0% per day. The streptokinase-infused membranes were demonstrated to release the protein in a controlled manner, with ~90% of the enzyme molecules retaining their activity. The rate of streptokinase release from the membranes was in the range of 0.01–0.07 mg/cm2 per day. The polymer films did not exert any short-term toxic effects on the cells cultivated de novo on the film surface. The mitotic index of cells growing on the surface of polymer films was ~1.5%. The implantation of the synthesized polymers in animals – in the form of film samples and as a component of the coating of nitinol stents – had no complications during the postoperative period. The histological examination of the implant-surrounding tissues did not reveal any abnormalities. When the polymers were implanted as separate film samples, only traces of PGLA were detected in the tissues two months after the surgery. The implantation of stents coated with the streptokinase-infused polymers resulted in the formation of a mature and thick connective-tissue capsule. Thus, novel biodegradable PLGA-based polymer membranes have been synthesized and tested in this work – membranes which possess the necessary mechanical properties and are capable of a sustained and directional release of high-molecular biological compounds.



中文翻译:

基于不同分子量的PLGA聚合物的可生物降解的支架涂料,可稳定释放血栓性酶链激酶

工作描述了基于聚新颖的生物可降解的聚合物膜的合成(乳酸--乙醇酸(PLGA)以及对其理化性质的测试。已显示合成的膜具有必要的机械性能,并能够持续和定向释放大型生物大分子,尤其是链激酶的分子(分子量为47 kDa)。链激酶是具有高溶栓活性的药物。所开发的技术可以合成相对伸长率为25%至165%,抗拉强度为20至55 MPa的膜。膜是可生物降解的;等渗溶液中聚合物的降解速率为每天0.5–1.0%。已证明注入链激酶的膜以受控方式释放蛋白质,约90%的酶分子保持其活性。2每天。聚合物膜对膜表面上从头培养的细胞没有任何短期毒性作用。在聚合物薄膜表面生长的细胞的有丝分裂指数约为1.5%。合成聚合物以薄膜样品的形式以及作为镍钛合金支架涂层的一部分植入动物体内,在术后没有并发症。植入物周围组织的组织学检查未发现任何异常。当将聚合物作为单独的薄膜样品植入时,在术后两个月的组织中仅检测到痕量的PGLA。用注入链激酶的聚合物包被的支架的植入导致成熟而厚的结缔组织囊的形成。从而,

更新日期:2020-03-09
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