Doxorubicin-loaded poly(ethylene glycol)-poly(β-benzyl-l-aspartate) copolymer micelles:: their pharmaceutical characteristics and biological significance
Doxorubicin-loaded poly(ethylene glycol)-poly(β-benzyl-l-aspartate) copolymer micelles:: their pharmaceutical characteristics and biological significance
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DOI：
10.1016/s0168-3659(99)00133-9
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发表时间：
2000-02-14
影响因子：
10.8
通讯作者：
Kwon, GS
中科院分区：
文献类型：
--
作者：
Kataoka, K;Matsumoto, T;Kwon, GS
采用0 /w乳液法制备聚（乙二醇）-聚（β -苄基- l-天冬氨酸）嵌段共聚物（PEG-PBLA），以15 ~ 20 w/w%的载药量将阿霉素（DOX）物理负载到胶束中。负载dox的胶束在尺寸上分布狭窄，直径约为50-70 nm。DOX的二聚体衍生物和DOX本身被包裹在胶团中，前者由于其低水溶性和可能通过pi-pi堆叠与PBLA片段的苯基残基相互作用而提高了胶团的稳定性。DOX化合物从胶束中的释放分两个阶段进行：最初的快速释放，随后是DOX的缓慢和持久释放阶段。将周围pH从7.4降低到5.0可以加速DOX的释放，这表明DOX从胶束中释放是pH敏感的。使用PEG-PBLA胶束作为载体，DOX的血液循环得到了显著改善，这可能是由于网状内皮系统通过空间稳定机制减少了胶束的摄取。最后，与静脉注射的游离DOX相比，载于胶束中的DOX对小鼠C26肿瘤的抗肿瘤活性要高得多，这表明PEG-PBLA胶束作为一种可用于调节药物递送的长循环载体系统具有很大的前景。(C) 2000 Elsevier Science B.V.版权所有
Doxorubicin (DOX) was physically loaded into micelles prepared from poly(ethylene glycol)-poly(beta-benzyl-L-aspartate) block copolymer (PEG-PBLA) by an o/w emulsion method with a substantial drug loading level (15 to 20 w/w%). DOX-loaded micelles were narrowly distributed in size with diameters of approximately 50-70 nm. Dimer derivatives of DOX as well as DOX itself were revealed to be entrapped in the micelle, the former seems to improve micelle stability due to its low water solubility and possible interaction with benzyl residues of PBLA segments through pi-pi stacking. Release of DOX compounds from the micelles proceeded in two stages: an initial rapid release was followed by a stage of slow and long-lasting release of DOX. Acceleration of DOX release can be obtained by lowering the surrounding pH from 7.4 to 5.0, suggesting a pH-sensitive release of DOX from the micelles. A remarkable improvement in blood circulation of DOX was achieved by use of PEG-PBLA micelle as a carrier presumably due to the reduced reticuloendothelial system uptake of the micelles through a steric stabilization mechanism. Finally, DOX loaded in the micelle showed a considerably higher antitumor activity compared to free DOX against mouse C26 tumor by i.v. injection, indicating a promising feature for PEG-PBLA micelle as a long-circulating carrier system useful in modulated drug delivery. (C) 2000 Elsevier Science B.V. All rights reserved.