Brushed block copolymer micelles with pH-sensitive pendant groups for controlled drug delivery

Hyun Jin Lee, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Purpose: To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. Methods: The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-decanone, and 2-dodecanone) through an acid-labile hydrazone linker to poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers. Results: Only block copolymers with 2-hexanone and 2-octanone (PEG-HEX and PEG-OCT) formed micelles with a clinically relevant size (< 50 nm in diameter), low critical micelle concentration (CMC, < 20 μM), and drug entrapment yields (approximately 5 wt.%). Both micelles degraded in aqueous solutions in a pH-dependent manner, while the degradation was accelerated in an acidic condition (pH 5.0) in comparison to pH 7.4. Despite these similar properties, PEG-OCT micelles controlled the entrapment and pH-dependent release of a hydrophobic drug most efficiently, without altering particle size, shape, and stability. The molecular weight of PEG (12 kDa vs 5 kDa) induced no change in pH-controlled drug release rates of PEG-OCT micelles. Conclusion: Acid-labile small aliphatic pendant groups are useful to control the entrapment and release of a hydrophobic drug physically entrapped in the core of brushed block copolymer micelles.

Original languageEnglish
Pages (from-to)2077-2086
Number of pages10
JournalPharmaceutical Research
Volume30
Issue number8
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
This research is supported by the Kentucky Lung Cancer Research Program.

Keywords

  • block copolymers
  • drug delivery
  • nanoparticles
  • pH-controlled release
  • polymer micelles

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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