Achieving High Drug Loading and Sustained Release of Hydrophobic Drugs in Hydrogels through In Situ Crystallization
Achieving High Drug Loading and Sustained Release of Hydrophobic Drugs in Hydrogels through In Situ Crystallization
复制标题
通过原位结晶实现水凝胶中疏水性药物的高载药量和缓释
DOI：
10.1002/mabi.201600299
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发表时间：
2017-03-01
影响因子：
4.6
通讯作者：
Ding, Jiandong
中科院分区：
文献类型：
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作者：
Ci, Tianyuan;Shen, Yuning;Ding, Jiandong
水凝胶作为药物的缓释载体时，疏水药物载药量不足是一个经典问题。在此，提出了一种装载大量疏水药物的策略。将抗癌药物10-羟基喜树碱应用于聚(D)、(L)-乳酸-乙醇酸共聚-b-乙二醇聚(D)、(L)-乳酸-乙醇酸热凝胶中。该药物可溶于碱性介质，但不溶于中性/酸性介质。在酸性共聚溶液中加入碱性药物溶液后，触发结晶。浓缩的共聚物水溶液在加热时经历了溶胶-凝胶转变，比结晶更快。结果形成了大量均匀分散的药物微晶。体外和体内实验表明，该制剂载药量高，缓释效果好，抗肿瘤效果好，不良反应少。该系统解决了在水凝胶中配制疏水药物的挑战，并促进了将药物以可溶-不溶的方式过渡到物质环境中。
Inadequate drug loading of hydrophobic drugs is a classic problem when hydrogels are utilized assustained-release carriers of drugs. Herein, a strategy to load plenty of hydrophobic drugs is presented. The antitumor drug 10-hydroxycamptothecin in the thermogel ofpoly((D),(L)- lactic acid-co-glycolic acid)-b-poly( ethylene glycol)-b-poly((D),(L)-lactic acid-co-glycolic acid) is employed. The drug is soluble in an alkaline medium, yet insoluble in a neutral/acidic medium. The crystallization is triggered after adding an alkaline drug solution into an acidic copolymer solution. The concentrated copolymer aqueous solution undergoes a sol-gel transition upon heating, faster than the crystallization. As a result, plenty of evenly dispersed drug microcrystals are formed. The in vitro and in vivo experiments indicate both high drug loading and sustained release with enhanced antitumor efficacy and reduced adverse effects. The system resolves the challenge in formulation of hydrophobic drugs in hydrogels, and is stimulating for encapsulating drugs with a soluble-insoluble transition into a material environment.