New self-assembling polyaspartylhydrazide copolymer micelles for anticancer drug delivery
New self-assembling polyaspartylhydrazide copolymer micelles for anticancer drug delivery
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DOI：
10.1016/j.ijpharm.2010.06.021
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发表时间：
2010-08-30
影响因子：
5.8
通讯作者：
Giammona, Gaetano
中科院分区：
文献类型：
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作者：
Licciardi, Mariano;Cavallaro, Gennara;Giammona, Gaetano
以水溶性聚丙烯酰肼（PAHy）为原料，通过在聚合物主链上同时接枝亲水性的PEG（2000）链和疏水性的棕榈酸（C-16）链段，合成了一种新型的两亲性共聚物，并通过2D H-1/C-13 NMR实验对PAHy-PEC 2000-C-16共聚物的结构进行了表征。16共聚物在水介质中表现出自组装的能力，得到核-壳结构，从而潜在地用于包封和溶解疏水性药物。通过2D H-1 NMR NOESY实验研究了胶束核壳结构的形成。C-16和PAHy部分质子的交叉峰的存在，表明这两个结构域非常接近，形成了胶束核。通过荧光技术在水中测定了PAHy-PEG（2000）-C-16两亲性接枝共聚物的临界聚集浓度（CAC）值，并且证明PAHy-PEG（2000）-C-16胶束非常适合作为高度疏水分子的胶束载体。因此，抗癌药物他莫昔芬，用作模型疏水分子，的PAHy-PEG（2000）-C-16胶束中，获得了约3000倍的药物溶解度增加的透射电子显微镜（TEM）观察显示由PAHy-PEG（2000）-C-16共聚物形成的胶束的球形形态，平均直径为约30 nm，这也通过动态光散射（DLS）研究证实。最后，在人乳腺癌细胞（MCF-7）上进行体外细胞活力研究，测试负载他莫昔芬的PAHy-PEC 2000-C-16胶束的药理学活性。与不同药物浓度下的游离他莫昔芬相比，证明负载他莫昔芬的PAHy-PEG（2000）-C-16胶束表现出浓度依赖性细胞毒性活性（C）2010 Elsevier B. V.保留所有权利。
A new amphiphilic copolymer have been synthesized starting from the hydrosoluble polyaspartylhydrazide (PAHy) polymer, by grafting both hydrophilic PEG(2000) chains and hydrophobic palmitic acid (C-16) moieties on polymer backbone, and the structure of obtained PAHy-PEC2000-C-16 copolymer have been characterized by 2D H-1/C-13 NMR experiments PAHy-PEC2000-C-16 copolymer showed the ability of self-assembling in aqueous media giving a core-shell structure and resulted potentially useful for encapsulating and dissolving hydrophobic drug. The formation of micellar core-shell structure has been investigated by 2D H-1 NMR NOESY experiments The presence of cross-peaks for protons of C-16 and PAHy portions, Indicated that the two domains are in close proximity forming micelle core The critical aggregation concentration (CAC) values of PAHy-PEG(2000)-C-16 amphiphilic graft copolymer was determined in water by fluorescence technique, and it was demonstrated that PAHy-PEG(2000)-C-16 micelles are well suited to be micellar vehicle of highly hydrophobic molecules Therefore, anticancer drug tamoxifen, used as a model hydrophobic molecule, was loaded into PAHy-PEG(2000)-C-16 micelles obtaining an increase of drug solubility of about 3000 times Transmission electron microscopy (TEM) observations showed the spherical morphology of micelles formed by PAHy-PEG(2000)-C-16 copolymer with a mean diameter of about 30 nm, as confirmed also by dynamic light scattering (DLS) studies. Finally, in vitro cell viability studies were carried out on human breast cancer cells (MCF-7) testing the pharmacological activity of tamoxifen-loaded PAHy-PEC2000-C-16 micelles. in comparison with free tamoxifen at different drug concentrations, demonstrating that tamoxifen-loaded PAHy-PEG(2000)-C-16 micelles exhibited a concentration-dependent cytotoxic activity (C) 2010 Elsevier B.V. All rights reserved.