Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles

Yingchao Han; Zhijian He; Anita Schulz; Tatiana K. Bronich; Rainer Jordan; Robert Luxenhofer; Alexander V. Kabanov

doi:10.1021/mp300159u

Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles

Yingchao Han, Zhijian He, Anita Schulz, Tatiana K. Bronich, Rainer Jordan, Robert Luxenhofer, Alexander V. Kabanov

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

Abstract

Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multidrug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt % drug per final formulation. Multidrug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.

Original language	English (US)
Pages (from-to)	2302-2313
Number of pages	12
Journal	Molecular Pharmaceutics
Volume	9
Issue number	8
DOIs	https://doi.org/10.1021/mp300159u
State	Published - Aug 6 2012

Keywords

block copolymer
combination therapy
drug delivery
drug formulation
nanomedicine
polymeric micelles
synergistic cytotoxicity

ASJC Scopus subject areas

Molecular Medicine
Pharmaceutical Science
Drug Discovery

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title = "Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles",

abstract = "Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multidrug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt % drug per final formulation. Multidrug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.",

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AU - He, Zhijian

AU - Schulz, Anita

AU - Bronich, Tatiana K.

AU - Jordan, Rainer

AU - Luxenhofer, Robert

AU - Kabanov, Alexander V.

PY - 2012/8/6

Y1 - 2012/8/6

N2 - Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multidrug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt % drug per final formulation. Multidrug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.

AB - Many effective drugs for cancer treatment are poorly water-soluble. In combination chemotherapy, needed excipients in additive formulations are often toxic and restrict their applications in clinical intervention. Here, we report on amphiphilic poly(2-oxazoline)s (POx) micelles as a promising high capacity delivery platform for multidrug cancer chemotherapy. A variety of binary and ternary drugs combinations of paclitaxel (PTX), docetaxel (DTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), etoposide (ETO) and bortezomib (BTZ) were solubilized in defined polymeric micelles achieving unprecedented high total loading capacities of up to 50 wt % drug per final formulation. Multidrug loaded POx micelles showed enhanced stability in comparison to single-drug loaded micelles. Drug ratio dependent synergistic cytotoxicity of micellar ETO/17-AAG was observed in MCF-7 cancer cells and of micellar BTZ/17-AAG in MCF-7, PC3, MDA-MB-231 and HepG2 cells.

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KW - nanomedicine

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KW - synergistic cytotoxicity

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Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles

Abstract

Keywords

ASJC Scopus subject areas

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