LOW SWELLING, CROSS-LINKED GUAR AND ITS POTENTIAL USE AS COLON-SPECIFIC DRUG CARRIER

Purpose. (a) To reduce the swelling properties of guar gum (GG) by cro sslinking it with glutaraldehyde (GA), while maintaining its degradati on properties in the presence of typical colonic enzymes, (b) to chara cterize the modified GG and to examine its degradation properties in v itro and in vivo, and (c) to assess, by drug probes with different wat er solubilities, the potential of the crosslinked GG to serve as a col on-specific drug carrier. Methods. GG was crosslinked with increasing amounts of GA under acidic conditions to obtain different products wit h increasing crosslinking densities. These products were characterized by measuring (a) their swelling properties in simulated gastric and i ntestinal fluids, (b) their crosslinking densities, (c) the release ki netics of three different drugs: sodium salicylate (SS), indomethacin (Indo) and budesonide (Bud) from the crosslinked products into buffer solutions, with or without a mixture of galactomannanase and alpha-gal actosidase, and (d) their in vivo degradation in the cecum of consciou s rats with and without antibiotic treatment. Results. Significant red uction in GG swelling properties, in both simulated gastric and intest inal fluids, was accomplished by its crosslinking with GA. The crossli nking density of the modified GG products was GA concentration-depende nt. The release of SS from crosslinked GG discs was completed within 1 20 minutes. During the same period of time and for more than 10 hours the release of Indo and Bud was negligible. The release rate of the la tter two drugs was enhanced when galactomannanase and alpha-galactosid ase were added to the dissolution media. Discs made of the crosslinked GG were implanted in the cecum of rats and their degradation was asse ssed after 4 days. The extent of degradation was dependent on the amou nt of GA used for the crosslinking. After 4 days the same discs were r ecovered intact from rats exposed to antibiotic treatment and from sim ulated gastric and intestinal fluids. Conclusions. Reducing the enormo us swelling of GG by crosslinking it with GA resulted in a biodegradab le hydrogel which was able to retain poorly water soluble drugs, such as Indo and BUD, but not highly water soluble drugs, such as SS, in ar tificial gastrointestinal fluids. A variety of hydrogels with increasi ng crosslinking densities were produced and tested for their potential use as colon-specific drug platforms in vitro and in vivo. Their perf ormance did not depend on creating physical barriers by means of compr ession.