Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles.
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.
Center for Drug Delivery and Nanomedicine and Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198-5830, United States.
Yingchao
Y
Han
Zhijian
Z
He
Anita
A
Schulz
Tatiana K
TK
Bronich
Rainer
R
Jordan
Robert
R
Luxenhofer
Alexander V
AV
Kabanov
D000970:Antineoplastic Agents / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005047:Etoposide / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000494:pharmacology; D008823:Micelles; D010080:Oxazoles / Q000737:chemistry*; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D016227:Benzoquinones; D004337:Drug Carriers; D047029:Lactams, Macrocyclic; D008823:Micelles; D010080:Oxazoles; D043823:Taxoids; C577913:poly(2-oxazoline); D000077143:Docetaxel; C112765:tanespimycin; D005047:Etoposide