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

被引：220

作者：

Shin, Ho-Chul ^{[1
]}

Alani, Adam W. G. ^{[1
]}

Rao, Deepa A. ^{[2
]}

Rockich, Nicole C. ^{[1
]}

Kwon, Glen S. ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA

[2] Drake Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Des Moines, IA 50265 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2009年 / 140卷 / 03期

关键词：

Polymeric micelle; Drug solubilization; Combination drug therapy; Cremophor EL; Heat shock protein 90 inhibitor; PHASE-II TRIAL; IN-VITRO; TANESPIMYCIN; 17-AAG; TOPOISOMERASE-II; CREMOPHOR-FREE; BREAST-CANCER; LUNG-CANCER; PACLITAXEL; HSP90; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN;

D O I：

10.1016/j.jconrel.2009.04.024

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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-6-PLA micelles. Combinations of PTX/17-AAG, ETO/17-AAG, DCTX/17-AAG and PTX/ETO/17-AAG were also solubilized in PEG-6-PLA micelles. PEG-6-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-6-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-6-PLA micelles offer a promising alternative for combination drug therapy without formulation related side effects. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：294 / 300

页数：7

共 41 条

[1] Butitaxel analogues: Synthesis and structure-activity relationships [J].

Ali, SM ;

Hoemann, MZ ;

Aube, J ;

Georg, GI ;

Mitscher, LA ;

Jayasinghe, LR .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (02) :236-241

[2] Disposition of drugs in block copolymer micelle delivery systems - From discovery to recovery [J].

Aliabadi, Hamidreza Montazeri ;

Shahin, Mostafa ;

Brocks, Dion R. ;

Lavasanifar, Afsaneh .

CLINICAL PHARMACOKINETICS, 2008, 47 (10) :619-634

[3] Micelles of methoxy poly(ethylene oxide)-b-poly(ε-caprolactone) as vehicles for the solubilization and controlled delivery of Cyclosporine A [J].

Aliabadi, HM ;

Mahmud, A ;

Sharifabadi, AD ;

Lavasanifar, A .

JOURNAL OF CONTROLLED RELEASE, 2005, 104 (02) :301-311

[4] The topoisomerase II-Hsp90 complex: A new chemotherapeutic target? [J].

Barker, CR ;

Hamlett, J ;

Pennington, SR ;

Burrows, F ;

Lundgren, K ;

Lough, R ;

Watson, AJM ;

Jenkins, JR .

INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (11) :2685-2693

[5] β-Lapachone-containing PEG-PLA polymer micelles as novel nanotherapeutics against NQO1-overexpres sing tumor cells [J].

Blanco, Elvin ;

Bey, Erik A. ;

Dong, Ying ;

Weinberg, Brent D. ;

Sutton, Damon M. ;

Boothman, David A. ;

Gao, Jinming .

JOURNAL OF CONTROLLED RELEASE, 2007, 122 (03) :365-374

[6] Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo Forster resonance energy transfer imaging [J].

Chen, Hongtao ;

Kim, Sungwon ;

He, Wei ;

Wang, Haifeng ;

Low, Philip S. ;

Park, Kinam ;

Cheng, Ji-Xin .

LANGMUIR, 2008, 24 (10) :5213-5217

[7] SUSPECTED ANAPHYLACTIC REACTION TO CREMOPHOR EL [J].

DYE, D ;

WATKINS, J .

BRITISH MEDICAL JOURNAL, 1980, 280 (6228) :1353-1353

[8]

Finley R.S., 1998, Concepts in oncology therapeutics, V2nd, P87

[9] In vitro release of the mTOR inhibitor rapamycin from poly(ethylene glycol)-b-poly(ε-caprolactone) micelles [J].

Forrest, ML ;

Won, CY ;

Malick, AW ;

Kwon, GS .

JOURNAL OF CONTROLLED RELEASE, 2006, 110 (02) :370-377

[10] Etoposide: Four decades of development of a topoisomerase II inhibitor [J].

Hande, KR .

EUROPEAN JOURNAL OF CANCER, 1998, 34 (10) :1514-1521

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