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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.

SUBMITTER: Han Y 

PROVIDER: S-EPMC3534837 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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

Han Yingchao Y   He Zhijian Z   Schulz Anita A   Bronich Tatiana K TK   Jordan Rainer R   Luxenhofer Robert R   Kabanov Alexander V AV  

Molecular pharmaceutics 20120628 8

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), e  ...[more]

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