pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: A comparative study with micelles
pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: A comparative study with micelles
复制标题
用于触发释放抗癌药物的 pH 敏感可降解聚合物囊泡：与胶束的比较研究
DOI：
10.1016/j.jconrel.2009.09.023
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发表时间：
2010-02-25
影响因子：
10.8
通讯作者：
Zhong, Zhiyuan
中科院分区：
文献类型：
--
作者：
Chen, Wei;Meng, Fenghua;Zhong, Zhiyuan
基于聚乙二醇（PEG）和酸不稳定聚碳酸酯聚（2,4,6-三甲氧基亚苄基季戊四醇碳酸酯）（PTMBPEC）的二嵌段共聚物制备了pH敏感的可降解聚合物囊泡和胶束。 PEG(1.9k)-PTMBPEC(6k) 的聚合物囊泡平均尺寸为 100-200 nm。聚合物囊泡的缩醛与 PEG(5k)-PTMBPEC(5.8k) 胶束的缩醛相似，虽然在 pH 7.4 下稳定，但在弱酸性 pH 4.0 和 5.0 下容易快速水解，半衰期分别为 0.5 和 3 d。缩醛水解导致聚合物囊泡的尺寸显着增加，在 pH 4.0 下 24 小时内达到超过 1000 nm。药物封装研究表明，聚合物囊泡能够同时负载紫杉醇（PTX，疏水性）和盐酸阿霉素（DOX中心点HCl，亲水性），而胶束仅负载PTX。值得注意的是，聚合物囊泡对 M 的载药效率低于胶束（30.0-37.7% vs 61.4-65.2%）。体外释放研究表明，PTX 和 DOX 中心点 HCl 从聚合物囊泡中的释放高度依赖于 pH 值，即。与生理 pH 值相比，在 4.0 和 5.0 的弱酸性 pH 值下药物释放明显更快。此外，在其他相同的条件下，与胶束中的 M 释放相比，观察到 M 从聚合物囊泡中释放的释放速率要高得多。这些 pH 敏感的纳米级可降解聚合物囊泡在癌症联合治疗方面具有广阔的前景。 (C) 2009 Elsevier B.V. 保留所有权利。
pH-Sensitive degradable polymersomes and micelles were prepared based on diblock copolymer of poly (ethylene glycol) (PEG) and an acid-labile polycarbonate, poly(2,4,6-trimethoxybenzylidenepentaerythritol carbonate) (PTMBPEC). Polymersomes of PEG( 1.9k)-PTMBPEC(6k) revealed average sizes of 100-200 nm. The acetals of polymersomes, similar to those of PEG(5k)-PTMBPEC(5.8k) micelles, though stable at pH 7.4 were prone to fast hydrolysis at mildly acidic pH of 4.0 and 5.0, with half lives of 0.5 and 3 d, respectively. The acetal hydrolysis resulted in significant size increase of polymersomes, to over 1000 nm in 24 h at pH 4.0. Drug encapsulation studies revealed that polymersomes were able to simultaneously load paclitaxel (PTX, hydrophobic) and doxorubicin hydrochloride (DOX center dot HCl, hydrophilic), whereas micelles loaded PTX only. Notably, polymersomes showed lower drug loading efficiencies for M than micelles (30.0-37.7% versus 61.4-65.2%). The in vitro release studies demonstrated that release of PTX and DOX center dot HCl from polymersomes was highly pH-dependent, i-e. significantly faster drug release at mildly acidic pH of 4.0 and 5.0 compared to physiological pH. Furthermore, much higher release rates were observed for M release from the polymersomes compared to that from the micelles under otherwise the same conditions. These pH-sensitive nano-sized degradable polymersomes hold great promise for combination therapy for cancers. (C) 2009 Elsevier B.V. All rights reserved.