In this study, we have synthesized dextran hydrogels by the crosslinking reactions of dextran with some selective Cl-, and N-containing functional monomers, such as epichlorohydrin (ECH), N,N 0 -methylenebisacrylamide (MBAm), and glutaraldehyde (GA). Crosslinking reactions were carried out in the basic aqueous solutions (2.8N NaOH) at 25-508C. The optimum conditions for effective crosslinking, i.e., temperature, crosslinking time, and amount of crosslinker, were determined for each system. The hydrogel discs of 3 mm diameter and 1.5 mm thickness were subjected to a number of Tris-buffer solutions of desired pH (2.0-9.0) at 378C. Swelling kinetics of the hydrogels were evaluated with second-order swelling model. The pH-dependent swelling of hydrogels was strongly influenced by the functional group of crosslinker and crosslinker content. While the hydrogels prepared with ECH and MBAm shows higher swelling ability at basic medium than that of acidic medium, GA-containing hydrogels exhibited just the opposite behavior. Mesh sizes (x) and average molecular weights between crosslinks (M c ) were estimated from swelling data using the Flory-Rehner theory. Characterization studies were completed by Fourier transform infrared spectroscopy and thermal gravimetric analysis.
Hydrogels synthesized from a polysaccharide-based polymer, dextran, in the presence of two crosslinking agents, N,N 0 -methylenebisacrylamide and epichlorohydrin, were evaluated for the oral colon-specific delivery of polypeptide drugs. These novel dextran hydrogels had significantly greater swelling ratios than recently developed dextran hydrogels. A model protein, bovine serum albumin, was loaded into 50% (by weight) crosslinker-containing dextran hydrogels in two ways: during the crosslinking reaction and by a soaking method. The loading capacity was varied between 22 and 25 mg/g of dry gel, depending on the loading procedure. In vitro release experiments were performed with a simulated gastrointestinal system in the presence and absence of dextranase. The diffusion exponents were calculated by means of a semiempirical power-law equation for the release of protein from swellable hydrogel discs. Bovine serum albumin was mainly released by Fickian diffusion, and this indicated that its hydrodynamic diameter (7.7 nm) was smaller than the hydrogel mesh size ($19 nm). The release of bovine serum albumin from both hydrogel types was substantially higher than expected, especially in the presence of dextranase, and this was attributed to the high swellability of the hydrogels.
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