A stimuli-responsive hydrogel for doxorubicin delivery

Mahrokh Dadsetan, Zen Liu, Matthias Pumberger, Catalina Vallejo Giraldo, Terry Ruesink, Lichun Lu, Michael J. Yaszemski

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion-exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.

Original languageEnglish (US)
Pages (from-to)8051-8062
Number of pages12
JournalBiomaterials
Volume31
Issue number31
DOIs
StatePublished - Nov 2010

Keywords

  • Chemotherapy
  • Controlled drug release
  • Drug delivery
  • Hydrogel
  • In vitro test

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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