Poly(2-oxazoline) block copolymer based formulations of taxanes: Effect of copolymer and drug structure, concentration, and environmental factors

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Youngee Seo - , University of North Carolina at Chapel Hill (Author)
  • Anita Schulz - , Chair of Macromolecular Chemistry (Author)
  • Yingchao Han - , University of Nebraska Medical Center (Author)
  • Zhijian He - , University of North Carolina at Chapel Hill (Author)
  • Herdis Bludau - , Chair of Macromolecular Chemistry (Author)
  • Xiaomeng Wan - , University of North Carolina at Chapel Hill (Author)
  • Jing Tong - , University of Nebraska Medical Center (Author)
  • Tatiana K. Bronich - , University of Nebraska Medical Center (Author)
  • Marina Sokolsky - , University of North Carolina at Chapel Hill (Author)
  • Robert Luxenhofer - , University of Würzburg (Author)
  • Rainer Jordan - , Chair of Macromolecular Chemistry (Author)
  • Alexander V. Kabanov - , University of North Carolina at Chapel Hill, Lomonosov Moscow State University (Author)

Abstract

Many current nanoformulations of taxanes are hampered by low drug-loading capacity and unfavorable physicochemical characteristics such as large particles size (>100nm) and/or low size uniformity. We have previously reported on taxane nanoformulations, based on poly(2-oxazoline) polymeric micelles that display an extremely high taxane loading capacity (>40%w/w) and particle size below 50nm. Previous work was based on a triblock copolymer having poly(2-butyl-2-oxazoline) as the hydrophobic block and poly(2-methyl-2-oxazoline) as the hydrophilic blocks. This paper explores the effects of various formulation parameters such as (i) the drug and polymer structure; (ii) the drug and polymer concentration; and (iii) the composition of aqueous medium on the solubilization behavior and physicochemical properties of the resulting formulations. In addition, in vitro anticancer activity is reported. Despite numerous variations of the hydrophobicity, polarity or addition of aromatic residues in the hydrophobic core, the triblock copolymer with the poly(2-butyl-2-oxazoline) block remains the polymer with the highest drug-loading capacity. Notably, the formulation was easily scalable with uncompromised encapsulation efficacy, loading capacity, and physicochemical properties. The taxane formulations were stable upon storage (water, saline, and dextrose solution) for 1-2weeks and could be lyophilized and re-dispersed without compromising the formulation properties. Furthermore, the micelles remained stable upon dilution. The drug-loaded poly(2-oxazoline) micelles showed high toxicity against several cancer cell lines. Taken together, these results underscore the potential of poly(2-oxazoline) micelles as formulation excipient for taxanes and possibly other hydrophobic drugs.

Details

Original languageEnglish
Pages (from-to)837-850
Number of pages14
JournalPolymers for Advanced Technologies
Volume26
Issue number7
Publication statusPublished - 1 Jul 2015
Peer-reviewedYes

External IDs

Scopus 84931828846

Keywords

Sustainable Development Goals

Keywords

  • block copolymer micelles, poly(2-oxazoline), paclitaxel, nanomedicine, drug delivery, docetaxel