Enzyme-digestible hydrogels for oral drug delivery

The application of controlled release technology to oral drug delivery has had minimal success due to (1) the relatively short and variable gastrointestinal (GI) residence time and (2) the variability in the type and quantity of lumenal contents which can influence drug release rates. Enzyme-digestible hydrogels were synthesized as a gastric retention device to control gastric emptying for long-term oral drug delivery. The swelling, mechanical, and degradation properties of the hydrogel were controlled by varying the concentration of crosslinking agent (functionalized albumin, FA) in the monomer solution, the degree of modification on the FA, or the concentration of chemical initiator in the monomer solution. The incorporation of a model drug, flavin mononucleotide (FMN), into hydrogels of suitable size and integrity led to prolonged FMN levels in the blood for up to 54 h. Based on these findings, we synthesized new hydrogels using interpenetrating networks which were more suitable for human application. Drug incorporation into hydrogels was studied using freeze drying and electrophoresis. The uniform incorporation of dextromethorphan hydrobromide into enzyme-digestible hydrogels was achieved by using the freeze drying process to remove water from swollen, drug-containing hydrogels. An electrophoretic apparatus was used to incorporate protein drugs into hydrogels. The application of current across the face of a hydrogel improved the loading efficiency by increasing the degree of protein incorporation in the gel and by reducing the loading time. The use of hydrogels for the delivery oral vaccines to cattle was also studied. Hydrogels were used as a carrier to protect antigens against the harsh environment of the first stomach (rumen) in ruminants and to provide sustained release of antigens to the lymphoid tissue of the small intestine. Approximately 60% of the administered hydrogels moved rapidly from the first stomach into the second stomach of the ruminant within 45 min. Hydrogels were found to release a model antigen, chromium-ethylenediamine tetracetic acid (Cr-EDTA), for up to 96 h to the small intestine. Cattle receiving leukotoxin-loaded hydrogels mounted a significantly greater immune response to virulent pasteurella haemolytica as compared to non-vaccinated control cattle. (Abstract shortened by UMI.