Biodegradable hydrogels for time-controlled release of tethered peptides or proteins

Biomacromolecules. 2010 Feb 8;11(2):496-504. doi: 10.1021/bm901235g.

Abstract

Tethering drug substances to a gel network is an effective way of controlling the release kinetics of hydrogel-based drug delivery systems. Here, we report on in situ forming, biodegradable hydrogels that allow for the covalent attachment of peptides or proteins. Hydrogels were prepared by step-growth polymerization of branched poly(ethylene glycol). The gel strength ranged from 1075 to 2435 Pa; the degradation time varied between 24 and 120 h. Fluorescence recovery after photobleaching showed that fluorescently labeled bovine serum albumin (FITC-BSA) was successfully bound to the gel network during gel formation. Within 168 h, the mobility of the tethered molecules gradually increased due to polymer degradation. Using FITC-BSA and lysozyme as model proteins, we showed the potential of the developed hydrogels for time-controlled release. The obtained release profiles had a sigmoidal shape and matched the degradation profile very well; protein release was complete after 96 h.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Cattle
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / pharmacokinetics
  • Hydrogels / administration & dosage
  • Hydrogels / pharmacokinetics*
  • Muramidase / administration & dosage
  • Muramidase / pharmacokinetics
  • Peptides / administration & dosage
  • Peptides / pharmacokinetics*
  • Proteins / administration & dosage
  • Proteins / pharmacokinetics*
  • Serum Albumin, Bovine / administration & dosage
  • Serum Albumin, Bovine / pharmacokinetics

Substances

  • Delayed-Action Preparations
  • Hydrogels
  • Peptides
  • Proteins
  • fluorescein isothiocyanate bovine serum albumin
  • Serum Albumin, Bovine
  • Muramidase
  • Fluorescein-5-isothiocyanate