Preparation of camptothecin-loaded polymeric micelles and evaluation of their incorporation and circulation stability
Preparation of camptothecin-loaded polymeric micelles and evaluation of their incorporation and circulation stability
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DOI：
10.1016/j.ijpharm.2005.10.030
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发表时间：
2006-02-03
影响因子：
5.8
通讯作者：
Maitani, Y
中科院分区：
文献类型：
--
作者：
Watanabe, M;Kawano, K;Maitani, Y
为了改善其在水溶液中的溶解性和在生物体液中的稳定性，将CPT物理负载到聚合物胶束中。聚合物胶束由不同的聚乙二醇-聚天冬氨酸嵌段共聚物(PEGP(Asp(R)组成。根据嵌段共聚物的化学结构，分别用凝胶渗透色谱测定胶束中的CPT和用高效液相色谱法测定静脉注射后CPT的浓度来评价CPT胶束的包封性和循环稳定性。与体外相比，CPT胶束在体内的稳定性更大程度上依赖于聚合物中的苄基酯的数量和聚乙二醇的长度。以聚乙二醇5000(Mw)、27个天冬氨酸单元和57-75%天冬氨酸的苄基酯化反应，得到了稳定的CPT胶束配方。这种CPT胶束的血液清除值比不稳定胶束低约17倍。由于血液循环的延长，负载CPT的胶束有可能被输送到肿瘤部位。(C)2005 Elsevier B.V.保留所有权利。
To improve its aqueous solubility and stability in biological fluid, CPT was physically loaded in polymeric micelles. Polymeric micelles were composed of various poly(ethylene glycol)-poly(aspartate ester) block copolymers (PEG-P(Asp(R))). The incorporation and circulation stability of CPT micelles were evaluated by measuring the CPT in micelle using gel-permeation chromatography and by CPT concentration measurement after intravenous injection using HPLC, respectively, in terms of chemical structure of block copolymers. The stability of CPT-loaded micelles in vivo depended on the amount of benzyl esters, and length of PEG in the polymers to a greater degree than it did in vitro. A stable formulation of CPT-loaded micelles was obtained using PEG-P(Asp) with PEG of 5000 (MW), 27 Asp units, and 57-75% benzyl esterification of Asp residue. This CPT-loaded micelles showed about a 17-fold lower blood clearance value than unstable micelles. The CPT-loaded micelles are potentially delivered to tumor sites owing to an extended circulation in the blood stream. (c) 2005 Elsevier B.V. All rights reserved.