Preparation and In Vitro Evaluation of Novel Poly(anhydride-ester)-Based Amphiphilic Copolymer Curcumin-Loaded Micelles
Preparation and In Vitro Evaluation of Novel Poly(anhydride-ester)-Based Amphiphilic Copolymer Curcumin-Loaded Micelles
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新型聚酸酐酯基两亲性共聚物姜黄素胶束的制备及体外评价
DOI：
10.1166/jbn.2014.1789
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发表时间：
2014-02-01
影响因子：
2.9
通讯作者：
Huang, Shengtang
中科院分区：
文献类型：
--
作者：
Lv, Li;Shen, Yuanyuan;Huang, Shengtang
以α，ω-乙酸酐封端的聚L-乳酸（PLA）为原料，通过熔融缩聚得到聚乙二醇甲酯（PEG）和聚丙二醇酯（PEG-b），再经酯化反应合成了PAE-b-PEG共聚物，并用核磁共振氢谱（H-NMR）和凝胶渗透色谱（GPC）进行了表征。由此获得的两种聚（酸酐-酯）-b-聚（乙二醇）（表示为PAE-b-PEG（2k）和PAE-b-PEG（5 k））可在水中自组装形成流体动力学直径为92.5和97.5nm的胶束，分别高于它们的临界胶束浓度3.78和2.36 μ g/mL。采用固体分散法制备了姜黄素PAE-b-PEG（2k）和PAE-b-PEG（5 k）胶束，其对姜黄素的包封率约为7%（w/w）。胶束的直径稳定5天。姜黄素在pH 5.0时比在pH 7.4时从胶束中释放得更快。姜黄素从胶束中释放在一个快速的速度在最初的12小时，随后由零级释放在随后的200小时，无论是在pH 5.0和7.4。姜黄素负载PAE-b-PEG（2k）和PAE-b-PEG（5 k）胶束对HeLa细胞的IC 50值分别为12.41和15.31 μ g/mL，低于游离姜黄素的IC 50值（25.90 μ g/mL）。PAE-b-PEG（2k）胶束比PAE-b-PEG（5 k）胶束更快地被HeLa细胞吸收。姜黄素胶束可诱导HeLa细胞发生G2/M期阻滞和凋亡。
Novel poly(anhydride-ester)-b-poly(ethylene glycol) copolymers (PAE-b-PEGs) were synthesized by esterization of methyl poly(ethylene glycol) and poly(anhydride-ester), which were obtained by the melt polycondensation of alpha,omega-acetic anhydride-terminated poly(L-lactic acid), and characterized by H-1-NMR and gel permeation chromatography. The two poly(anhydride-ester)-b-poly(ethylene glycols) (denoted as PAE-b-PEG(2k) and PAE-b-PEG(5k)) thus obtained can self-assemble in water to form micelles with hydrodynamic diameters of 92.5 and 97.5 nm above their critical micelle concentrations of 3.78 and 2.36 mu g/mL, respectively. The curcumin-loaded PAE-b-PEG(2k) and PAE-b-PEG(5k) micelles were prepared by the solid dispersion method, and they could encapsulate approximately 7% (w/w) curcumin. The diameters of the micelles were stable for 5 days. Curcumin is released faster from the micelles at pH 5.0 than at pH 7.4. Curcumin is released from the micelles at a fast rate during the initial 12 h, followed by a zero-order release during the subsequent 200 h, both at pH 5.0 and 7.4. The IC50 values of the curcumin-loaded PAE-b-PEG(2k) and PAE-b-PEG(5k) micelles against HeLa cells are 12.41 and 15.31 mu g/mL, respectively, which is lower than that of free curcumin (25.90 mu g/mL). The PAE-b-PEG(2k) micelles are taken up faster than the PAE-b-PEG(5k) micelles by HeLa cells. Curcumin-loaded micelles can induce G(2)/M phase cell cycle arrest and apoptosis of HeLa cells.