School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China.
Biomaterials. 2012 Sep;33(26):6273-83. doi: 10.1016/j.biomaterials.2012.05.025. Epub 2012 Jun 12.
A series of amphiphilic pH-responsive poly (ethylene glycol) methyl ether-b-(poly lactic acid-co-poly (β-amino esters)) (MPEG-b-(PLA-co-PAE)) block copolymers with different PLA/PAE ratios were designed and synthesized via a Michael-type step polymerization. The molecular structures of the copolymers were confirmed with (1)H NMR and gel permeation chromatography (GPC). These amphiphilic copolymers were shown to self-assemble into core/shell micelles in aqueous solution at low concentrations, and their critical micelle concentrations (CMC) in water were 1.2-9.5 mg/L. The pH-responsive PAE segment was insoluble at pH 7.4, but it became positively charged and soluble via protonation of amino groups at pH lower than 6.5. The average particle size and zeta potential of micelles increased from 180 nm and 15 mV to 220 nm and 40 mV, respectively, when the pH decreased from 7.4 to 5.0. Doxorubicin (DOX) was loaded into the core of these micelles with a high drug loading of 18%. The in vitro DOX release from the micelles was significantly accelerated when solution pH decreased from 7.4 to 5.0. DOX release in the first 10 h appeared to follow Fickian diffusion mechanism. Toxicity test showed that the copolymers had low toxicity whereas the DOX-loaded micelles remained high cytotoxicity for HepG2 cells. The results indicate the pH-sensitive MPEG-b-(PLA-co-PAE) micelle may be a potential hydrophobic drug delivery carrier for cancer targeting therapy with sustained release.
设计并合成了一系列不同 PLA/PAE 比例的两亲性 pH 响应性聚乙二醇甲基醚-b-(聚乳酸-co-聚(β-氨基酯))(MPEG-b-(PLA-co-PAE))嵌段共聚物，通过迈克尔型逐步聚合得到。用（1）H NMR 和凝胶渗透色谱（GPC）对共聚物的分子结构进行了确认。这些两亲性共聚物在低浓度下在水溶液中自组装成核/壳型胶束，其在水中的临界胶束浓度（CMC）为 1.2-9.5mg/L。pH 响应性 PAE 段在 pH 7.4 时不溶，但在 pH 低于 6.5 时通过氨基质子化而带正电并溶解。当 pH 从 7.4 降至 5.0 时，胶束的平均粒径和zeta 电位分别从 180nm 和 15mV 增加到 220nm 和 40mV。阿霉素（DOX）被包载于胶束的核中，载药量高达 18%。当溶液 pH 从 7.4 降至 5.0 时，DOX 从胶束中的释放明显加速。前 10h 的 DOX 释放似乎遵循菲克扩散机制。毒性试验表明，共聚物毒性低，而载 DOX 的胶束对 HepG2 细胞仍保持高细胞毒性。结果表明，pH 敏感的 MPEG-b-(PLA-co-PAE)胶束可能是一种具有持续释放的用于癌症靶向治疗的潜在疏水性药物载体。
