Polymeric micellar pH-sensitive drug delivery system for doxorubicin
Polymeric micellar pH-sensitive drug delivery system for doxorubicin
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DOI：
10.1016/j.jconrel.2004.11.017
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发表时间：
2005-03-02
影响因子：
10.8
通讯作者：
Ulbrich, K
中科院分区：
文献类型：
--
作者：
Hruby, M;Konák, C;Ulbrich, K
描述了一种新的聚合物胶束ph敏感系统，用于递送阿霉素（DOX）。用两亲二嵌段共聚物在水溶液中自组装制备了聚合物胶束。共聚物由生物相容性亲水性聚环氧乙烷（PEO）嵌段和含有共价结合的蒽环类抗生素DOX的疏水嵌段组成。以聚环氧乙烷单甲醚钠盐为宏观引发剂，烯丙基缩水甘油醚为功能单体，采用阴离子开环聚合法制备了分子量分布极窄（M-w/M-n = 1.05）的聚环氧乙烷-聚烯丙基缩水甘油醚嵌段共聚物（PEO-PAGE）。共聚物通过添加乳酸磺酰甲酯的活性双键进行共价改性。所得酯随后与水合肼反应生成聚合物肼。肼与DOX偶联，在药物和载体之间形成ph敏感的腙键。所得的共轭物含有约3 wt.% DOX，在磷酸盐缓冲盐水中形成R-h(a)=104 nm的胶束。37℃缓冲液孵育后，pH 5.0（接近内体pH值，24 h内释放43% DOX）比pH 7.4（血浆pH值，24 h内释放16% DOX）释放更快。即使在水溶液中培养的胶束中DOX的释放达到平稳期后，DOX和载体之间的腙键的断裂仍在继续。(c) 2004 Elsevier B.V.版权所有
A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (M-w/M-n ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl, ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive a hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with R-h(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached. (c) 2004 Elsevier B.V. All rights reserved.