Poly(2-oxazoline)-based core cross-linked star polymers: synthesis and drug delivery applications

Nedah Alkattan, Noura Alasmael, Viko Ladelta, Niveen M. Khashab*, Nikos Hadjichristidis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Poly(2-oxazoline)s (POxs) are promising platforms for drug delivery applications due to their biocompatibility and stealth properties. In addition, the use of core cross-linked star (CCS) polymers based on POxs is expected to enhance drug encapsulation and release performances. In this study, we employed the “arm-first” strategy to synthesize a series of amphiphilic CCS [poly(2-methyl-2-oxazoline)]n-block-poly(2,2′-(1,4-phenylene)bis-2-oxazoline)-cross-link/copolymer-(2-n-butyl-2-oxazoline)s (PMeOx)n-b-P(PhBisOx-cl/co-ButOx)s by using microwave-assisted cationic ring-opening polymerization (CROP). First, PMeOx, as the hydrophilic arm, was synthesized by CROP of MeOx using methyl tosylate as the initiator. Subsequently, the living PMeOx was used as the macroinitiator to initiate the copolymerization/core-crosslinking reaction of ButOx and PhBisOx to form CCS POxs having a hydrophobic core. The molecular structures of the resulting CCS POxs were characterized by size exclusion chromatography and nuclear magnetic resonance spectroscopy. The CCS POxs were loaded with the anti-cancer drug doxorubicin (DOX), and the loading was detected by UV-vis spectrometry, dynamic light scattering, and transmission electron microscopy. In vitro studies showed that DOX release at pH 5.2 was faster than that at pH 7.1. The in vitro cytotoxicity study using HeLa cells revealed that the neat CCS POxs are compatible with the cells. In contrast, the DOX-loaded CCS POxs exhibited a cytotoxic effect in a concentration-dependent manner in HeLa cells, which strongly supports that the CSS POxs are potential candidates for drug delivery applications.

Original languageEnglish (US)
Pages (from-to)2794-2803
Number of pages10
JournalNanoscale Advances
Issue number10
StatePublished - Apr 5 2023

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Chemistry(all)
  • Materials Science(all)
  • Engineering(all)


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