Synthesis and in vitro evaluation of a pH-sensitive PLA-PEG-folate based polymeric micelle for controlled delivery of docetaxel
Synthesis and in vitro evaluation of a pH-sensitive PLA-PEG-folate based polymeric micelle for controlled delivery of docetaxel
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DOI：
10.1016/j.colsurfb.2014.01.015
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发表时间：
2014-04-01
影响因子：
5.8
通讯作者：
Gilani, Kambiz
中科院分区：
文献类型：
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作者：
Hami, Zahra;Amini, Mohsen;Gilani, Kambiz
通过酸不稳定的腙键合成了pH响应的紫杉醇-聚乳酸（PLA）-聚乙二醇（PEG）胶束制剂。乙酰丙酸（LEV）用作多西他赛（DTX）和肼之间的连接体。通过将叶酸偶联到PEG片段实现DTX的靶向递送。该聚合物胶束的直径约为181 nm，临界胶束浓度为5.18 μ g/ml。DTX从胶束中以pH依赖的方式释放。结果表明，在pH 5.0和pH 7.4的聚合物胶束中的DTX释放的显着差异。使用甲基四唑（MTT）、中性红（NR）和乳酸脱氢酶（LDH）的细胞毒性测定表明，与游离DTX相比，含有纳米缀合物的药物的细胞毒性活性降低，这似乎有助于药物从胶束中的持续释放。基于这些结果，预期这种pH响应性纳米缀合物有希望作为用于靶向递送抗癌剂的有用载体。(C)2014爱思唯尔有限公司版权所有。
pH-responsive docetaxel-conjugated poly (lactic acid) (PLA)-polyethyleneglycol (PEG) micellar formulation was synthesized via acid labile hydrazone linkage. Levulinic acid (LEV) was used as a linker between docetaxel (DTX) and hydrazine. Targeted delivery of DTX was achieved by conjugation of folate to PEG segment. The DTX conjugated polymeric micelles were about 181 nm in diameter and their critical micelle concentration was 5.18 mu g/ml. DTX was released from micelles in a pH-dependent manner. The results showed a significant difference in DTX release from polymeric micelles at pH 5.0 and pH 7.4. Cytotoxicity assays using methyl tetrazolium (MTT), neutral red (NR) and lactate dehydrogenase (LDH) demonstrated a decreased cytotoxic activity of the drug containing nanoconjugate compared with free DTX that appears to be contributed to the sustained release of drug from micelles. Based on these results, it is expected that this pH-responsive nanoconjugate is promising as a useful carrier for targeted delivery of anticancer agents. (C) 2014 Elsevier B.V. All rights reserved.