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) |
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Pages (from-to) | 2302-2313 |
Number of pages | 12 |
Journal | Molecular Pharmaceutics |
Volume | 9 |
Issue number | 8 |
DOIs | |
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