Y-Shaped mPEG-PLA Cabazitaxel Conjugates: Well-Controlled Synthesis by Organocatalytic Approach and Self-Assembly into Interface Drug-Loaded Core-Corona Nanoparticles
Y-Shaped mPEG-PLA Cabazitaxel Conjugates: Well-Controlled Synthesis by Organocatalytic Approach and Self-Assembly into Interface Drug-Loaded Core-Corona Nanoparticles
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DOI：
10.1021/bm400161g
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发表时间：
2013-04-01
影响因子：
6.2
通讯作者：
Bourissou, Didier
中科院分区：
文献类型：
--
作者：
Bensaid, Fethi;du Boullay, Olivier Thillaye;Bourissou, Didier
一个定义明确的聚（乙二醇）甲基醚-b-聚（乳酸）共聚物（mPEG-PLA）具有一个新的，Y形，结构与两个嵌段之间的羟基官能团已被制备和彻底的特点。然后将官能共聚物容易地偶联至二甘醇酰-卡巴他赛。所得共聚物缀合物在水悬浮液中组装成稳定且单分散的纳米颗粒（NPs）。显示共聚物缀合物的结构影响药物在纳米颗粒内的空间分布。通过在D2 O中对纳米颗粒进行变温NMR分析，发现卡巴他赛具有Y形结构，定位于纳米颗粒的疏水PLA核心和亲水mPEG冠的界面处。初步的体外释放研究表明依赖于共聚物缀合物的结构。这种新的方法提供了有前途的前景，精细地调整聚合物纳米颗粒中的活性成分的位置。
A well-defined poly(ethylene glycol) methyl ether-b-poly(lactic acid) copolymer (mPEG-PLA) featuring a new, Y-shaped, architecture with a hydroxyl functional group between the two blocks has been prepared and thoroughly characterized. The functional copolymer was then readily coupled to diglycolyl-cabazitaxel. The resulting copolymer conjugates assembled into stable and monodisperse nanoparticles (NPs) in aqueous suspension. The architecture of the copolymer conjugate is shown to impact the spatial distribution of the drug within the nanoparticles. With the Y-shaped architecture, cabazitaxel was found localized at the interface of the hydrophobic PLA core and the hydrophilic mPEG corona of the NPs, as substantiated by variable temperature NMR analysis of the nanoparticles in D2O. Preliminary in vitro release studies reveal dependence on the architecture of the copolymer conjugate. This new approach offers promising perspectives to finely tune the position of the active ingredient in polymeric nanoparticles.