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 journalArticle

73 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2302-2313
Number of pages12
JournalMolecular Pharmaceutics
Volume9
Issue number8
DOIs
StatePublished - Aug 6 2012

Fingerprint

tanespimycin
Micelles
docetaxel
Etoposide
Pharmaceutical Preparations
Neoplasms
Water Purification
Excipients
Poisons
MCF-7 Cells
Hep G2 Cells
Drug Combinations
Paclitaxel
Combination Drug Therapy
Drug Therapy
poly(2-oxazoline)

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles. / Han, Yingchao; He, Zhijian; Schulz, Anita; Bronich, Tatiana K; Jordan, Rainer; Luxenhofer, Robert; Kabanov, Alexander V.

In: Molecular Pharmaceutics, Vol. 9, No. 8, 06.08.2012, p. 2302-2313.

Research output: Contribution to journalArticle

Han, Yingchao ; He, Zhijian ; Schulz, Anita ; Bronich, Tatiana K ; Jordan, Rainer ; Luxenhofer, Robert ; Kabanov, Alexander V. / Synergistic combinations of multiple chemotherapeutic agents in high capacity poly(2-oxazoline) micelles. In: Molecular Pharmaceutics. 2012 ; Vol. 9, No. 8. pp. 2302-2313.
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