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Release of recombinant human interleukin-2 from dextran-based hydrogels
J A Cadée1, C J de Groot, W Jiskoot
1Faculty of Pharmacy, Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, The Netherlands.
Summary
This study investigated recombinant human interleukin-2 (rhIL-2) release from dextran hydrogels. Release rates were controlled by hydrogel crosslink density and degradation, with bioactive rhIL-2 monomer released effectively.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Polymer Chemistry
Background:
- Dextran-based hydrogels are promising for controlled protein release.
- Understanding release kinetics is crucial for therapeutic applications.
Purpose of the Study:
- To investigate the release of recombinant human interleukin-2 (rhIL-2) from non-degradable methacrylated dextran (dex-MA) and degradable dex-lactate-HEMA hydrogels.
- To evaluate the impact of crosslink density and hydrogel degradation on rhIL-2 release profiles.
- To assess the biological activity and form of released rhIL-2.
Main Methods:
- Synthesis of dex-MA, dex-HEMA, and dex-lactate-HEMA hydrogels with varying crosslink densities.
- In vitro release studies of rhIL-2 from hydrogels under physiological conditions.
- Analysis of release kinetics (Fickian diffusion, degradation-controlled).
- Assessment of rhIL-2 biological activity post-release.
Main Results:
- Increasing crosslink density reduced rhIL-2 release from both dex-MA and degradable hydrogels.
- Non-degradable dex-MA hydrogels showed Fickian diffusion or complete entrapment based on water content.
- Degradable dex-lactate-HEMA hydrogels exhibited near zero-order release over 5-15 days.
- Released rhIL-2 was primarily monomeric and retained significant biological activity.
Conclusions:
- Hydrogel crosslink density and degradation characteristics effectively modulate rhIL-2 release.
- Degradable dex-lactate-HEMA hydrogels offer controlled, sustained release of bioactive rhIL-2.
- These dextran-based hydrogels are suitable for delivering functional proteins like rhIL-2.