Acid-labile core cross-linked micelles for pH-triggered release of antitumor drugs

Biomacromolecules. 2008 Jul;9(7):1826-36. doi: 10.1021/bm800043n. Epub 2008 Jun 20.

Abstract

Micelles of a model amphiphilic block copolymer, poly(hydroxyethyl acrylate)-block-poly(n-butyl acrylate) (PHEA-b-PBA), synthesized via the RAFT polymerization were cross-linked by copolymerization of a degradable cross-linker from the living RAFT-end groups of PBA chains, yielding a cross-linked core without affecting significantly the original micelle size. The cross-linker incorporation into the micelles was evidenced via physicochemical analysis of the copolymer unimers formed upon acidic cleavage of the cross-linked micelles. High doxorubicin loading capacities (60 wt %) were obtained. Hydrolysis of less than half of the cross-links in the core was found to be sufficient to release doxorubicin faster at acidic pH compared to neutral pH. The system represents the first example of core-cross-linked micelles that can be destabilized (potentially both above and below CMC) by the pH-dependent cleavage of the cross-links and the subsequent polarity change in the core to enable the release of hydrophobic drugs entrapped inside the micelle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylates
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Cross-Linking Reagents / chemistry*
  • Doxorubicin / administration & dosage
  • Drug Delivery Systems / methods*
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Micelles*
  • Polyhydroxyethyl Methacrylate / analogs & derivatives
  • Polymers

Substances

  • Acrylates
  • Antineoplastic Agents
  • Cross-Linking Reagents
  • Micelles
  • Polymers
  • poly(n-butyl acrylate)
  • Polyhydroxyethyl Methacrylate
  • poly(2-hydroxyethyl acrylate)
  • Doxorubicin