Poloxamer188-聚L-乳酸质量比100%~200%复合电纺纤维对所载多西紫杉醇释放行为的影响  

Effect of Poloxamer188-polymer L-lactic Acid Mass Ratio of 100%~200%Composite Electrospun Fiber on Release Behavior of Incorporated Docetaxel

作　　者：王瑛颖 董欣 黄佳娜 张天 王浩 Wang Yingying;Dong Xin;Huang Jiana;Zhang Tian;Wang Hao(School of Pharmacy,Jinzhou Medical University,Jinzhou 121000 China;Qidu Pharmaceutical Industry,Zibo 255400 China)

机构地区：[1]锦州医科大学药学院,辽宁锦州121000 [2]齐都药业,山东淄博255400

出　　处：《锦州医科大学学报》2022年第1期10-16,共7页Journal of Jinzhou Medical University

基　　金：辽宁省药物作用与质量评价专业技术创新中心与辽宁省海洋生物活性物质重点实验室主任基金,项目编号:2020-06;辽宁省药物作用与质量评价工程技术研究中心主任基金,项目编号:2018110605;中国博士后基金资助项目,项目编号:2014M561187。

摘　　要：目的考察Poloxamer188复合量在100%~200%时,多西紫杉醇载量在2.5%、5%、10%时聚L-乳酸电纺纤维中多西紫杉醇的包裹和释放行为。方法将多西紫杉醇、Poloxamer188、聚L-乳酸共同溶解在二氯甲烷中形成均相溶液后静电纺丝,其中Poloxamer188的复合量设为聚L-乳酸质量的100%~200%,多西紫杉醇的载量设为聚L-乳酸质量的2.5%、5%、10%。扫描电子显微镜观察纤维形态,高效液相色谱法测定水释放介质中多西紫杉醇的含量,绘制释放曲线并以Peppas方程式对释放曲线进行拟合。结果所得产品均为微米级直径均匀无珠子结构的纤维。随着Poloxamer188复合量的增高,药物的百分释放量逐渐增高;随着多西紫杉醇载量的增高,药物的百分释放量逐渐降低。多西紫杉醇载量在2.5%时,在整个释放过程中其均以被增溶方式释放;多西紫杉醇载量在5%时,随着Poloxamer188复合量的增高,其释放初始阶段从有结晶状态逐渐转换到无结晶状态;多西紫杉醇载量在10%时,在释放初期仍然有结晶析出。多西紫杉醇的释放曲线可以被Pappas方程式拟合。Poloxamer188复合量200%,多西紫杉醇载药量2.5%时,药物最大百分释放量超过69.4%。结论Poloxamer188复合量为聚L-乳酸的100%~200%时,多西紫杉醇的载药量不同其释放状态有所区别,实验结果提示继续增高Poloxamer188的复合量可能会得到多西紫杉醇百分释放量更高且释放过程全部为增溶状态的聚L-乳酸电纺纤维。Objective To investigate the encapsulation and release behaviors of docetaxel in Poloxamer188 when the compound amount of docetaxel was 100%~200%and the amount of docetaxel was 2.5%,5%and 10%.Methods Docetaxel,Poloxamer188 and Poly-L-lactic acid were dissolved together in dichloromethane to form homogeneous solution and then electrospun.The compound amount of Poloxamer188 was set as 100%~200%of the mass of Poly-L-lactic acid.The dosage of docetaxel was set at 2.5%,5%and 10%of the mass of Poly-L-lactic acid.Fiber morphology was observed by scanning electron microscope.The conlent of docelaxel in water release mcdium was determined by HPLD.The release curve was plotted and fitted by Peppas equation.Results All the products are micrometer-grade fiber with uniform diameter and bead-free structure.With the increase of the compound amount of Poloxamer188,the percentage of drug release gradually increased.The percentage release of docetaxel decreased with the increase of docetaxel load.When docetaxel load was 2.5%,it was solubilized during the whole release process.When docetaxel loading was 5%,the initial release phase of Poloxamer188 was gradually transformed from crystalline state to non-crystalline state with the increase of the compound amount of Poloxamer188.When docetaxel loading was 10%,there was still crystallization at the initial release stage.The release curve of docetaxel can be fitted by Pappas equation.When Poloxamer188 combined with 200%and docetaxel loaded with 2.5%,the maximum percentage of drug release was more than 69.4%.Conclusion When the compound amount of Poloxamer188 is 100%~200%of Poly-L-lactic acid,the release state of docetaxel varies with the drug loading amount.The experimental results suggest that increasing the compound amount of Poloxamer188 may produce Poly-L-lactic acid electrospun fibers with higher percentage release of docetaxel and solubilized release process.

关 键 词：多西紫杉醇 电纺纤维 Poloxamer188 聚L-乳酸 控制释放 

分 类 号：R917[医药卫生—药物分析学]