Synergistic Combinations of Multiple Chemotherapeutic Agents in High Capacity Poly(2-oxazoline) Micelles
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- 作者：Yingchao Han ; Zhijian He ; Anita Schulz ; Tatiana K. Bronich ; Rainer Jordan ; Robert Luxenhofer ; Alexander V. Kabanov
- 刊名：Molecular Pharmaceutics
- 出版年：2012
- 出版时间：August 6, 2012
- 年：2012
- 卷：9
- 期：8
- 页码：2302-2313
- 全文大小：485K
- 年卷期：v.9,no.8(August 6, 2012)
- ISSN：1543-8392
文摘
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.