Polymeric micelles for the pH-dependent controlled, continuous low dose release of paclitaxel.
Polymeric micelles for the pH-dependent controlled, continuous low dose release of paclitaxel.
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紫杉醇的pH依赖性控制的低剂量释放的聚合物胶束。
DOI：
10.1016/j.biomaterials.2009.11.038
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发表时间：
2010-03
期刊：
影响因子：
14
通讯作者：
Kwon, Glen S.
中科院分区：
文献类型：
--
作者：
Alani, Adam W. G.;Bae, Younsoo;Rao, Deepa A.;Kwon, Glen S.
以乙酰丙酸（LEV）或4-乙酰基苯甲酸（4AB）为配体，通过酰肼键对聚乙二醇-嵌段-聚丁二酸-酰肼（PEG-p（Asp-Hyd））进行修饰。与接头缀合的紫杉醇（PTX）形成PEG-p（Asp-Hyd-LEV-PTX）和PEG-p（Asp-Hyd-4AB-PTX）。PEG-p（Asp-Hyd-LEV-PTX）和PEG-p（Asp-Hyd-4AB-PTX）分别组装成直径为42 nm和137 nm的单峰聚合物胶束。PEG-p（Asp-Hyd-LEV-PTX）和PEG-p（Asp-Hyd-4AB-PTX）以1：1和1：5的摩尔比组装成单峰混合聚合物胶束，其直径分别为85和113 nm。PEG-p（Asp-Hyd-LEV-PTX）胶束在pH 5.0下比在pH 7.4下释放LEV-PTX更快超过24小时。在pH 7.4下，以1：5比例混合的聚合物胶束显示LEV-PTX从PEG-p（Asp-Hyd-LEV-PTX）胶束释放没有差异。以1：5摩尔比混合的聚合物胶束在pH 5.0下逐渐释放LEV-PTX，而不释放4AB-PTX。PEG-p（Asp-Hyd-LEV-PTX）胶束和混合聚合物胶束对SK-0 V-3和MCF-7癌细胞系发挥相当的细胞毒性。总之，基于PEG-p（Asp-Hyd-LEV-PTX）和PEG-p（Asp-Hyd-4AB-PTX）的混合聚合物胶束为PTX的pH依赖性释放提供了前景，为调节其用于癌症治疗的药代动力学和药效学特性提供了新的前药策略。如果成功的话，该递送系统提供了紫杉醇的替代的新递送模式，其具有新的功效范围沿着实现该功效所需的最小合成框架。
Poly(ethylene glycol)-block-poly(aspartate-hydrazide) (PEG-p(Asp-Hyd)) was modified using either levulinic acid (LEV) or 4-acetyl benzoic acid (4AB) attached via hydrazone bonds. Paclitaxel (PTX) conjugated to the linkers formed PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX). PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) assemble into unimodal polymeric micelles with diameters of 42 nm and 137 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) at a 1:1 and 1:5 molar ratio assemble into unimodal mixed polymeric micelles with diameters of 85 and 113 nm, respectively. PEG-p(Asp-Hyd-LEV-PTX) micelles release LEV-PTX faster at pH 5.0 than at pH 7.4 over 24 hr. At pH 7.4 mixed polymeric micelles at 1:5 ratio show no difference in LEV-PTX release from PEG-p(Asp-Hyd-LEV-PTX) micelles. Mixed polymeric micelles at 1:5 molar ratio gradually releases LEV-PTX at pH 5.0, with no release of 4AB-PTX. PEG-p(Asp-Hyd-LEV-PTX) micelles and mixed polymeric micelles exert comparable cytotoxicity against SK-OV-3 and MCF-7 cancer cell lines. In summary, mixed polymeric micelles based on PEG-p(Asp-Hyd-LEV-PTX) and PEG-p(Asp-Hyd-4AB-PTX) offer prospects for pH-dependent release of PTX, offering a novel pro-drug strategy for adjusting its pharmacokinetic and pharmacodynamic properties for cancer therapy. If successful this delivery system offers an alternative new mode of delivery for paclitaxel with a new scope for its efficacy along with a minimal synthetic framework needed to accomplish this.
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影响因子：
4.7
作者：
YOKOYAMA, M;KWON, GS;KATAOKA, K
通讯作者：
KATAOKA, K
影响因子：
11.2
作者：
Ng, SSW;Figg, WD;Sparreboom, A
通讯作者：
Sparreboom, A
影响因子：
45.3
作者：
WEISS, RB;DONEHOWER, RC;LEYLANDJONES, B
通讯作者：
LEYLANDJONES, B
影响因子：
4.7
作者：
Bae, Younsoo;Nishiyama, Nobuhiro;Kataoka, Kazunori
通讯作者：
Kataoka, Kazunori
DOI：
10.1007/bf01964882
发表时间：
1977-01-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
LORENZ, W;REIMANN, HJ;DOENICKE, A
通讯作者：
DOENICKE, A