Colon-specific delivery of IgG from highly swellable dextran hydrogels: ın- vitro study
Abstract
Colonic drug delivery has gained increased importance for the delivery of peptide and protein drugs. In this study, the strategy is to investigate release of high molecular weight (MW) protein drugs from dextran-based hydrogels. The hydrogels were synthesized in the presence of crosslinking agents, N,N’-methylenebisacrylamide (MBAm) and epichlorohydrin (ECH). While dextran-MBAm hydrogels are having average equilibrium swelling ratios between 12.0 (at pH 2) and 14.0 (at pH 7), dextran-ECH hydrogels have values between 9.0 (at pH 2) and 12.5 (at pH 7). The model high molecular weight protein, immunoglobulin G (IgG), was loaded into the 50% (by weight) crosslinkercontaining dextran hydrogels by two ways, i.e. during the crosslinking reaction or by soaking method. The loading capacity was varied between 3.0 and 4.0 mg per g of dry gel by depending upon the loading procedure. In-vitro release experiments were performed in the simulated gastrointestinal system in the presence and absence of dextranase. The diffusion exponents were calculated by means of the semi-empirical power law equation indicated that IgG was mainly released by non-Fickian diffusion. The release of IgG from both hydrogels was substantially higher than that of similar systems especially in the presence of dextranase, which was attributed to the high swellability of the dextran hydrogels synthesized here. Colonic drug delivery has gained increased importance for the delivery of peptide and protein drugs. In this study, the strategy is to investigate release of high molecular weight (MW) protein drugs from dextran-based hydrogels. The hydrogels were synthesized in the presence of crosslinking agents, N,N’-methylenebisacrylamide (MBAm) and epichlorohydrin (ECH). While dextran-MBAm hydrogels are having average equilibrium swelling ratios between 12.0 (at pH 2) and 14.0 (at pH 7), dextran-ECH hydrogels have values between 9.0 (at pH 2) and 12.5 (at pH 7). The model high molecular weight protein, immunoglobulin G (IgG), was loaded into the 50% (by weight) crosslinkercontaining dextran hydrogels by two ways, i.e. during the crosslinking reaction or by soaking method. The loading capacity was varied between 3.0 and 4.0 mg per g of dry gel by depending upon the loading procedure. In-vitro release experiments were performed in the simulated gastrointestinal system in the presence and absence of dextranase. The diffusion exponents were calculated by means of the semi-empirical power law equation indicated that IgG was mainly released by non-Fickian diffusion. The release of IgG from both hydrogels was substantially higher than that of similar systems especially in the presence of dextranase, which was attributed to the high swellability of the dextran hydrogels synthesized here.
Source
Hacettepe Journal of Biology and ChemistryVolume
35Issue
3URI
http://www.trdizin.gov.tr/publication/paper/detail/TnprMk9EYzM=https://hdl.handle.net/20.500.12418/1879
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