Release of recombinant human interleukin-2 from dextran-based hydrogels

Publication Type:

Journal Article

Source:

Journal of Controlled Release, Volume 78, Number 1-3, pp. 1-13 (2002)

ISBN:

0168-3659

Keywords:

interleukin-2; lysozyme; biodegradable hydrogel; protein release; dextran; activated killer cells; biodegradable microspheres; glycidyl methacrylate; degradation kinetics; aqueous-solutions; protein; cancer; biocompatibility; immunotherapy; delivery

Abstract:

In this study, the release of recombinant human interleukin-2 (rhlL-2) from methacrylated dextran (dex-MA) and (lactate-)hydroxyethyl methacrylated dextran (dex-(lactate-)HEMA) hydrogels with varying crosslink density was investigated. Hydrogels derived from dex-MA are stable under physiological conditions (pH 7 and 37degreesC), whereas dex-HEMA and dex-lactate-HEMA hydrogels degrade due to the presence of hydrolytically sensitive esters in the crosslinks of the gels. The protein release profiles both the non-degradable and degradable dextran-based hydrogels showed that with increasing crosslink density of the get, the release of rhIL-2 decreases. From dex-MA hydrogels with an initial water content above 70%, the rhIL-2 release followed Fickian diffusion, whereas from gels with an initial water content of 70% or lower the protein was fully entrapped in the hydrogel meshes. In contrast with non-degradable dex-MA hydrogels, degradable dex-lactate-HEMA gels with comparable network characteristics (degree of methacrylate substitution and initial water content) showed an almost zero-order, degradation controlled release of rhIL-2 in a time period of 5-15 days. This paper demonstrates that the release of rhIL-2 from non-degradable dex-MA and degradable dex-lactate-HEMA gels can be modulated by the crosslink density and/or the degradation characteristics of the hydrogel. Importantly, rhIL-2 was mainly released as monomer from the hydrogels and with good retention of its biological activity. (C) 2002 Elsevier Science B.V. All rights reserved.

28/10/2009