聚乳酸/羟基乙酸可降解药物释放支架的探索-东南大学学报医学版

聚乳酸/羟基乙酸可降解药物释放支架的探索

作者：刘琳琳¹ 秦娟¹ 曾楚慧¹ 杜瑞杰¹ 陆骊工² 陈磊³ 滕皋军¹ 朱海东¹ 何仕诚¹

单位：1. 东南大学附属中大医院介入与血管外科, 江苏南京 210009;
2. 珠海市人民医院, 珠海市介入诊疗中心, 广东珠海 519000;
3. 苏州市立医院介入血管外科, 江苏苏州 215000]

分类号：R654;R454.9;R318

出版年·卷·期（页码）：2021·40·第三期（312-317）

摘要：

目的：探索聚乳酸/羟基乙酸（PLGA）材料作为制备生物可降解药物洗脱支架的生物安全性和可行性。方法：将PLGA与紫杉醇（PTX）混溶于二氯甲烷中，制备生物可降解载药PTX-PLGA膜。将制备的膜片置入磷酸盐缓冲液（pH=7.4/4.0）中进行体外降解及药物释放测试。用PTX-PLGA膜的浸提液培养提取的兔食管成纤维细胞，观察细胞的形态和增殖。结果：PTX-PLGA膜成功制备，PTX均匀溶解于PLGA膜中。膜片前4周质量损失分别为（23.76±1.62）%（pH=4.0）和（17.35±0.55）%（pH=7.4），不同载药量（10%、20%）的累积药物释放量分别为（137.26±11.35）μg·ml^-1（pH=4.0）、（102.73±6.94）μg·ml^-1（pH=7.4），（296.33±9.57）μg·ml^-1（pH=4.0）、（245.64±16.24）μg·ml^-1（pH=7.4）。用不同载药量（0、10%、20%）的膜片浸提液培养细胞48 h后，细胞凋亡率分别为（4.08±0.64）%、（18.62±1.19）%和（29.50±1.93）%（P<0.05）。结论：PLGA具有良好的生物兼容性，可在缓慢降解过程中稳定释放装载的PTX，促进成纤维细胞凋亡，可作为生物可降解载药支架的制备材料。

Objective: To explore the biosafety and feasibility of poly lactic acid-co-glycolic acid(PLGA) as the drug release platform of biodegradable drug-eluting stents. Methods: Paclitaxel-PLGA(PTX-PLGA) membrane was prepared by mixing PLGA with PTX in dichloromethane. The prepared diaphragms were placed in phosphate buffer solution(pH=7.4 or pH=4.0) for in vitro degradation and drug release tests. Fibroblasts of rabbit esophagus were cultured with extract of PTX-PLGA membrane to observe the morphology and proliferation of the cells. Results: PTX-PLGA was successfully prepared. PTX dissolved in the PLGA film uniformly. During the first 4 weeks, the average mass loss was (23.76±1.62)% (pH=4.0) and (17.35±0.55)%(pH=7.4), and the average cumulative drug releases(10%,20% of drug-loading)were(137.26±11.35)μg·ml^-1(pH=4.0),(102.73±6.94)μg·ml^-1(pH=7.4) and (296.33±9.57)μg·ml^-1(pH=4.0), (245.64±16.24)μg·ml^-1(pH=7.4), respectively. Cell apoptosis rates were (4.08±0.64)%, (18.62±1.19)% and (29.50±1.93)% after cell culture with membrane extracts for 48 h, respectively(P<0.05). Conclusion: PLGA demonstrates high biocompatibility, which subsequently degrade slowly and release loaded PTX and promote the apoptosis of fibroblasts in a stable manner. The preparation of biodegradable drug-loaded scaffolds could be applied to the treatment of benign stenosis.

参考文献：

[1] DE WIJKERSLOOTH L R, VLEGGAAR F P, SIERSEMA P D.Endoscopic management of difficult or recurrent esophageal strictures[J]. Am J Gastroenterol, 2011, 106(12):2080-2092.
[2] YANO T, YODA Y, NOMURA S, et al. Prospective trial of biodegradable stents for refractory benign esophageal strictures after curative treatment of esophageal cancer[J]. Gastrointest Endosc, 2017, 86(3):492-499.
[3] DZELETOVIC I, FLEISCHER D E, CROWELL M D, et al. Self dilation as a treatment for resistant benign esophageal strictures:outcome, technique, and quality of life assessment[J]. Dig Dis Sci, 2011, 56(2):435-440.
[4] SIERSEMA P D.How to approach a patient with refractory or recurrent benign esophageal stricture[J]. Gastroenterology, 2019, 156(1):7-10.
[5] HOURNEAUX D M E, TOMA K, GOH K L, et al. Stents for benign and malignant esophageal strictures[J]. Ann N Y Acad Sci, 2013, 1300:119-143.
[6] 吴斯蔚, 刘文静, 李超婧, 等. 食管支架在复杂性食管狭窄中的研究进展[J]. 介入放射学杂志, 2020, 29(8):842-846.
[7] WALTER D, VAN DEN BERG M W, HIRDES M M, et al. Dilation or biodegradable stent placement for recurrent benign esophageal strictures:a randomized controlled trial[J]. Endoscopy, 2018, 50(12):1146-1155.
[8] BICK B L, SONG L M, BUTTAR N S, et al. Stent-associated esophagorespiratory fistulas:incidence and risk factors[J]. Gastrointest Endosc, 2013, 77(2):181-189.
[9] DASARI B V, NEELY D, KENNEDY A, et al. The role of esophageal stents in the management of esophageal anastomotic leaks and benign esophageal perforations[J]. Ann Surg, 2014, 259(5):852-860.
[10] DONG T, ZHAO L, LIU L, et al. Biodegradable stent placement for recurrent or refractory benign esophageal stricture:a perspective from the East[J]. Endoscopy, 2019, 51(7):699.
[11] 韩雅玲.新型药物洗脱冠状动脉支架的临床应用[J]. 中华医学杂志, 2010, 90(30):2089-2091.
[12] 杨栋, 李宇罡, 王磊, 等. 生物可降解镁合金支架在兔体内的降解及生物安全性[J]. 中华医学杂志, 2017, 97(32):2533-2537.
[13] BUKALA J, BUSZMAN P P, MALACHOWSKI J, et al. Experimental tests, FEM constitutive modeling and validation of PLGA bioresorbable polymer for stent applications[J]. Materials (Basel), 2020, 13(8):2003.
[14] PAUCK R G, REDDY B D.Computational analysis of the radial mechanical performance of PLLA coronary artery stents[J]. Med Eng Phys, 2015, 37(1):7-12.
[15] IQBAL J, ONUMA Y, ORMISTON J, et al. Bioresorbable scaffolds:rationale, current status, challenges, and future[J]. Eur Heart J, 2014, 35(12):765-776.
[16] ONUMA Y, DUDEK D, THUESEN L, et al. Five-year clinical and functional multislice computed tomography angiographic results after coronary implantation of the fully resorbable polymeric everolimus-eluting scaffold in patients with de novo coronary artery disease:the ABSORB cohort A trial[J]. JACC Cardiovasc Interv, 2013, 6(10):999-1009.
[17] PETERSON G I, DOBRYNIN A V, BECKER M L.Biodegradable shape memory polymers in medicine[J]. Adv Healthc Mater, 2017, 6(21):1-16.
[18] HU T, YANG C, LIN S, et al. Biodegradable stents for coronary artery disease treatment:recent advances and future perspectives[J]. Mater Sci Eng C Mater Biol Appl, 2018, 91:163-178.
[19] MACHAN L.Clinical experience and applications of drug-eluting stents in the noncoronary vasculature, bile duct and esophagus[J]. Adv Drug Deliv Rev, 2006, 58(3):447-462.
[20] JEON S R, EUN S H, SHIM C S, et al. Effect of drug-eluting metal stents in benign esophageal stricture:an in vivo animal study[J]. Endoscopy, 2009, 41(5):449-456.
[21] YANG K, CAO J, YUAN T W, et al. Silicone-covered biodegradable magnesium stent for treating benign esophageal stricture in a rabbit model[J]. World J Gastroenterol, 2019, 25(25):3207-3217.
[22] WU Q, ZHU S, WANG L, et al. The microstructure and properties of cyclic extrusion compression treated Mg-Zn-Y-Nd alloy for vascular stent application[J]. J Mech Behav Biomed Mater, 2012, 8:1-7.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录