Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs

Biomaterials. 2015 Sep:63:146-57. doi: 10.1016/j.biomaterials.2015.06.008. Epub 2015 Jun 11.

Abstract

Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.

Keywords: Controlled drug release; Dextran; Hydrogels; Microstructure; Protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use
  • Cell Line, Tumor
  • Delayed-Action Preparations / chemistry*
  • Dextrans / chemistry*
  • Hepacivirus / drug effects
  • Hepacivirus / isolation & purification
  • Hepatitis C / drug therapy*
  • Hepatitis C / pathology
  • Humans
  • Hydrogels / chemistry*
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / chemistry
  • Interferon-alpha / pharmacokinetics
  • Interferon-alpha / therapeutic use
  • Liver / pathology
  • Liver / virology*
  • Male
  • Mice
  • Polyethylene Glycols / chemistry

Substances

  • Antiviral Agents
  • Delayed-Action Preparations
  • Dextrans
  • Hydrogels
  • Interferon-alpha
  • Polyethylene Glycols