In vitro and in vivo application of pH-sensitive colon-targeting polysaccharide hydrogel used for ulcerative colitis therapy

• Published in: Carbohydrate polymers Vol. 130; pp. 243 - 253
• Main Authors: You, Yu Cui, Dong, Ling Ya, Dong, Kai, Xu, Wei, Yan, Yan, Zhang, Lu, Wang, Ke, Xing, Feng Jian
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 05.10.2015
• Subjects: Alginates - chemistry; Amorphophallus - chemistry; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colon - drug effects; Colon - metabolism; Colon-targeting; Drug Delivery Systems; Glucuronic Acid - chemistry; Glycerol; Hexuronic Acids - chemistry; Hydrocortisone - administration & dosage; Hydrocortisone - analogs & derivatives; Hydrocortisone - pharmacokinetics; Hydrogel; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogen-Ion Concentration; Hydrophilic drug; Male; Mannans - chemistry; Peroxidase - metabolism; Polysaccharides, Bacterial - chemistry; Rats; Rats, Sprague-Dawley; Spleen and thymus index; Tissue Distribution; Glycerol; Hydrophilic drug; Spleen and thymus index; Hydrogel; Colon-targeting
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.03.075

These pictures are the schematic representation of synthesized HSS/K (KGM-XG-GLY-SA) hydrogel. Presence of glycerin prevents the rapid dissolution of material in higher pH of the intestine, ensuring a controlled release of the entrapped drug and shown a good colon-targeting characteristic for drugs, especially for hydrophilic drugs. In all, the developed HSS/KGM-XG-GLY-SA hydrogel as a colon-targeting vector might have greatly potential application in oral colon-specific drug delivery system (OCDDS). The aim of this study was to prepare, characterize novel types of pH-sensitive konjac gum–xanthan gum–glycerol–sodium alginate hydrogel (KGM–XG–GLY–SA hydrogel) allowing for the site-specific delivering of drugs to the colon and evaluate its colon-targeting characteristic. In this study, hydrophilic drug of hydrocortisone sodium succinate (HSS) was chosen as a model drug and successfully loaded in hydrogel without any organic solvent. In vitro investigations were carried out to evaluate its release process. The drug-loaded hydrogel shown good sustained release property that drugs release from test hydrogel was minimal at pH 1.2 (2h, 23.40%), pH 6.8 (4h, 25.88%), and significantly higher (4h, 70.20%) at pH 7.4. It is clear that adding glycerol in hydrogel as hysteresis preparation prevented the rapid dissolution of material in the higher pH of the intestine. Thus ensuring a controlled release of the entrapped drug. We studied the colonic-targeting behavior, in vivo toxicity test, pharmacokinetic study, features to reduce drug toxicity, and therapeutic effect of experimental UC of this preparation. All the results in vitro were shown that the K (KGM–XG–GLY–SA) hydrogels with glycerol had a good colon-targeting characteristic. In addition, results in vivo were indicated that K (KGM–XG–GLY–SA) hydrogel were nontoxic, reduced the spleen and thymus index, and had an obvious effect on the treatment of UC. Therefore, all results suggested that the developed HSS/KGM–XG–GLY–SA hydrogel (HSS-GEL) with glycerol as a colon-targeting vector might have greatly potential application in the UC healing.