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Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma.17-烯丙基氨基-17-去甲氧基格尔德霉素用于转移性黑色素瘤患者的II期试验。
Clin Cancer Res. 2008 Dec 15;14(24):8302-7. doi: 10.1158/1078-0432.CCR-08-1002.
2
Disposition of drugs in block copolymer micelle delivery systems: from discovery to recovery.药物在嵌段共聚物胶束递送系统中的处置：从发现到回收
Clin Pharmacokinet. 2008;47(10):619-34. doi: 10.2165/00003088-200847100-00001.
3
A cremophor-free formulation for tanespimycin (17-AAG) using PEO-b-PDLLA micelles: characterization and pharmacokinetics in rats.使用聚环氧乙烷-聚（D,L-丙交酯）（PEO-b-PDLLA）胶束的坦螺旋霉素（17-AAG）无聚氧乙烯蓖麻油制剂：大鼠体内的表征和药代动力学
J Pharm Sci. 2009 Apr;98(4):1577-86. doi: 10.1002/jps.21509.
4
Editorial for theme section on polymeric micelles for drug delivery.关于用于药物递送的聚合物胶束主题版块的社论。
Pharm Res. 2008 Sep;25(9):2053-5. doi: 10.1007/s11095-008-9644-x. Epub 2008 Jul 1.
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Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation.丙泊酚聚合物胶束的麻醉作用：一种新型水溶性丙泊酚制剂。
Br J Anaesth. 2008 Aug;101(2):186-93. doi: 10.1093/bja/aen147. Epub 2008 Jun 11.
6
A phase I study of 17-allylamino-17-demethoxygeldanamycin combined with paclitaxel in patients with advanced solid malignancies.17-烯丙基氨基-17-去甲氧基格尔德霉素联合紫杉醇治疗晚期实体恶性肿瘤患者的I期研究
Clin Cancer Res. 2008 Jun 1;14(11):3456-61. doi: 10.1158/1078-0432.CCR-07-5088.
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Poly (amino acid) micelle nanocarriers in preclinical and clinical studies.临床前和临床研究中的聚（氨基酸）胶束纳米载体
Adv Drug Deliv Rev. 2008 May 22;60(8):899-914. doi: 10.1016/j.addr.2007.11.010. Epub 2008 Feb 9.
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Block copolymer design for stable encapsulation of N-(4-hydroxyphenyl)retinamide into polymeric micelles in mice.用于在小鼠体内将N-(4-羟基苯基)视黄酰胺稳定包封到聚合物胶束中的嵌段共聚物设计。
Int J Pharm. 2008 Jun 5;357(1-2):318-22. doi: 10.1016/j.ijpharm.2008.01.044. Epub 2008 Feb 3.
9
Simulation modelling of human intestinal absorption using Caco-2 permeability and kinetic solubility data for early drug discovery.利用Caco-2细胞通透性和动力学溶解度数据进行人体肠道吸收的模拟建模，用于早期药物发现。
J Pharm Sci. 2008 Oct;97(10):4557-74. doi: 10.1002/jps.21305.
10
Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo forster resonance energy transfer imaging.体内荧光共振能量转移成像揭示循环聚乙二醇-聚（D，L-丙交酯）胶束中亲脂性药物的快速释放
Langmuir. 2008 May 20;24(10):5213-7. doi: 10.1021/la703570m. Epub 2008 Feb 8.

载多药聚合物胶束用于同时递送难溶性抗癌药物。

Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs.

机构信息

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.

出版信息

J Control Release. 2009 Dec 16;140(3):294-300. doi: 10.1016/j.jconrel.2009.04.024. Epub 2009 May 4.

DOI:10.1016/j.jconrel.2009.04.024
PMID:19409432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2787857/
Abstract

Current clinical and preclinical anticancer formulations are limited by their use of toxic excipients and stability issues upon combining different drug formulations. We have found that poly(ethylene glycol)-block-poly(d,l lactic acid) (PEG-b-PLA) micelles can deliver multiple poorly water-soluble drugs at clinically relevant doses. Paclitaxel (PTX), etoposide (ETO), docetaxel (DCTX) and 17-allylamino-17-demethyoxygeldanamycin (17-AAG) were solubilized individually in PEG-b-PLA micelles. Combinations of PTX/17-AAG, ETO/17-AAG, DCTX/17-AAG and PTX/ETO/17-AAG were also solubilized in PEG-b-PLA micelles. PEG-b-PLA micelles were characterized in terms of drug loading, size, stability and drug release. All anticancer agents in all combinations were all solubilized at the level of mg/mL and were stable for 24 h in the 2- and 3-drug combination PEG-b-PLA micelles. The stability of the 2- and 3-drug combination PEG-b-PLA micelles was due to the presence of 17-AAG. In vitro, t(1/2) values for 2- and 3-drug combination PEG-b-PLA micelles spanned 1-5 h. PEG-b-PLA micelles offer a promising alternative for combination drug therapy without formulation related side effects.

摘要

目前的临床前和临床抗癌制剂受到其使用的毒性赋形剂和不同药物制剂组合时的稳定性问题的限制。我们发现聚乙二醇-嵌段-聚（DL 乳酸）（PEG-b-PLA）胶束可以在临床相关剂量下递送多种水溶性差的药物。紫杉醇（PTX）、依托泊苷（ETO）、多西他赛（DCTX）和 17-烯丙基-17-去甲氧基格尔德霉素（17-AAG）分别在 PEG-b-PLA 胶束中溶解。PTX/17-AAG、ETO/17-AAG、DCTX/17-AAG 和 PTX/ETO/17-AAG 的组合也在 PEG-b-PLA 胶束中溶解。根据载药量、粒径、稳定性和药物释放情况对 PEG-b-PLA 胶束进行了表征。所有组合中的所有抗癌药物均以 mg/mL 的水平溶解，并且在 2 种和 3 种药物组合的 PEG-b-PLA 胶束中稳定 24 小时。2 种和 3 种药物组合的 PEG-b-PLA 胶束的稳定性归因于 17-AAG 的存在。体外，2 种和 3 种药物组合的 PEG-b-PLA 胶束的 t(1/2)值在 1-5 小时之间。PEG-b-PLA 胶束为无制剂相关副作用的联合药物治疗提供了一种有前途的替代方案。