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负载阿霉素的聚乙二醇/聚乳酸纳米颗粒的生物分布及抗肿瘤疗效

Bio-distribution and anti-tumor efficacy of PEG/PLA nano particles loaded doxorubicin.

作者信息

Yu J J, Lee H A, Kim J H, Kong W H, Kim Y, Cui Z Y, Park K G, Kim W S, Lee H G, Seo S W

机构信息

Medical Nano Element Development Center, Samsung Medical Center, Seoul, South Korea.

出版信息

J Drug Target. 2007 May;15(4):279-84. doi: 10.1080/10611860701357235.

Abstract

As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-L-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200-350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evaluate what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.

摘要

作为一种更有效的体内药物递送系统,人们已经探索并开发了几种将抗癌药物负载到可生物降解且生物相容的纳米颗粒上的方法。据推测,由于增强的渗透与滞留(EPR)效应,这些纳米颗粒的全身给药已被发现会导致纳米颗粒在实体瘤中积累。在本研究中,我们使用聚乙二醇(PEG)/聚-L-丙交酯(PLLA)二嵌段共聚物制备了纳米颗粒,并将阿霉素负载到这些纳米颗粒中(纳米阿霉素)。所制备的纳米颗粒在体外表现出药物的缓释动力学。为了追踪200 - 350纳米大小的纳米阿霉素颗粒在荷瘤(同基因肾细胞腺癌:RENCA)小鼠体内的生物分布,将羧基荧光素二乙酸琥珀酰亚胺酯(CFSE)负载到纳米颗粒中。纳米阿霉素优先在肿瘤中积累;然而,就其抗肿瘤疗效而言,与自由给药的阿霉素相比,它没有显示出任何显著优势。这一结果表明,在将药物递送系统与肿瘤EPR效应相结合的持续努力中,需要重新考虑和评估我们所使用的抗癌试剂类型。

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