Novel poly(2-oxazoline) block copolymer with aromatic heterocyclic side chains as a drug delivery platform

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

Contributors

  • Duhyeong Hwang - , University of North Carolina at Chapel Hill (Author)
  • Jacob D. Ramsey - , University of North Carolina at Chapel Hill (Author)
  • N. Makita - , University of North Carolina at Chapel Hill (Author)
  • Clemens Sachse - , Chair of Macromolecular Chemistry (Author)
  • Rainer Jordan - , Chair of Macromolecular Chemistry (Author)
  • Marina Sokolsky-Papkov - , University of North Carolina at Chapel Hill (Author)
  • Alexander V. Kabanov - , University of North Carolina at Chapel Hill, Lomonosov Moscow State University (Author)

Abstract

Here we report a novel poly(2-oxazoline)-based block copolymer with the aromatic heterocyclic side chains in one block, poly(2-methyl-2-oxazoline)-b-poly(2-N,N-dimethyl-1,3,5-triazine-2,4-diamine-6-ethyl-2-oxazoline) (PMeOx-PcBOx), and demonstrate its potential application as a drug delivery platform. The copolymer was synthesized via the condensation of N,N-dimethylbiguanide with the methyl ester side chain in poly(2-methoxycarboxyethyl-2-oxazoline) block (PMestOx) of the PMeOx-PMestOx diblock copolymer. We confirmed the N,N-dimethylbiguanide condensation with PMestOx and the complete conversion of the side chain to the N,N-dimethyl-1,3,5-triazine-2,4-diamine-6-ethyl moiety by NMR spectroscopy, MALDI-TOF mass spectroscopy, UV–Vis spectroscopy, and titration analysis. The PMeOx-PcBOx copolymer self-assemble into polymeric micelles in aqueous solution. Successful encapsulation into these micelles has been demonstrated for 1) several poorly soluble drugs, such as bruceantin and LY2109761, and 2) dichloro(1,2-diaminocyclohexane)platinum(II) (DachPt). The first class of drugs is incorporated possibly via hydrogen bonding and pi-pi interactions with the PcBOx side groups, while the second one is likely forms coordination bonds with the same side groups. The capability of this new copolymer to solubilize a uniquely diverse set of active pharmaceutical ingredients suggests potential applications in drug delivery.

Details

Original languageEnglish
Pages (from-to)261-271
Number of pages11
JournalJournal of Controlled Release
Volume307
Publication statusPublished - 10 Aug 2019
Peer-reviewedYes

External IDs

PubMed 31260756

Keywords

Keywords

  • Biguanide, Condensation, Coordination, Hydrogen bonding, Poly(2-oxaozoline), Polymeric micelles, Solubilization