title: Synthesis and properties of polysaccharide prodrugs of 5-aminosalicylic acid as potential colon-specific delivery systems.
abstract: The drug release of the polymer prodrugs of 5-aminosalicylic acid (5-ASA) was not only dependent on the property of the polymers but also dependent on the solubility of the prodrugs. We prepared several polysaccharide prodrugs of 5-ASA to examine the effect of solubility of prodrugs on the release characteristics of 5-ASA in the gastrointestinal contents of rats. The amide prodrug, chitosan-5-ASA (ChT-5-ASA), did not release the 5-ASA in the cecal and colonic contents. The ester prodrugs, hydroxypropyl cellulose-5-ASA (HPC-5-ASA), being poor solubility in 0.05mol/l acetic acid solution also did not release the 5-ASA in any of gastrointestinal contents of rats. Whereas the 5-ASA release from cyclodextrins-5-ASA (CyDs-5-ASA) in cecal and colonic contents was significantly higher than that in stomach and small intestine contents. And furthermore, with the decrease in the degree of substitution, the solubility of CyD-5-ASA increased, and the release of 5-ASA in the gastrointestinal contents was also higher at the same time interval of incubation. When the ratio of cyclodextrin (CyD) and 5-formylaminosalicylic acid (5-fASA), a precursor of 5-ASA prodrugs, was 1:10, CyD-5-ASA was very slightly soluble, and no release of 5-ASA was observed within 48h in gastrointestinal contents. The present results suggested that the ester prodrugs of 5-ASA with certain solubility could release 5-ASA in the cecal and colonic contents of rat.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Hao
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
authors.forename: Kazumi
authors.initials: K
authors.lastname: Danjo
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011134:Polysaccharides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011134:Polysaccharides; D011355:Prodrugs; D019804:Mesalamine