Release of recombinant human interleukin-2 from dextran-based hydrogels.
In this study, the release of recombinant human interleukin-2 (rhIL-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 37 degrees C), 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 gel, 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.
Cadée
J A
JA
Faculty of Pharmacy, Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, The Netherlands.
de Groot
C J
CJ
Jiskoot
W
W
den Otter
W
W
Hennink
W E
WE
D003911:Dextrans / Q000008:administration & dosage*; D004355:Drug Stability; D020100:Hydrogels; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000737:chemistry; D008689:Methacrylates / Q000008:administration & dosage*; D009113:Muramidase / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage
D003911:Dextrans; D020100:Hydrogels; D007376:Interleukin-2; D008689:Methacrylates; D011994:Recombinant Proteins; C005044:hydroxyethyl methacrylate; D009113:Muramidase