title: Oral sustained delivery of diclofenac sodium using calcium chondroitin sulfate matrix.
abstract: Chondroitin sulfate (CS) is a potential candidate for colon-specific drug carriers. However, the readily water-soluble nature limits its application as a solid-state drug-delivery vehicle. In this study, the CS formation of a polyelectrolyte complex (PEC) with Ca2+ (CS-Ca) was adapted to retain CS in a solid form for use in a drug-delivery system. Pre-treated CS with poly(ethylene glycol) diglycidyl ether (EX-810) followed by complexation with Ca2+ was also tested (CS-Ca-EX). Diclofenac sodium was used as a drug probe to evaluate the performance of the drug-release behavior of the complexes. The amount of diclofenac sodium released was higher in simulated intestinal fluid (SIF) than in simulated gastric fluid (SGF) due to the anionic groups on CS or the higher solubility of drug itself in PBS. The release profile of diclofenac sodium from CS-Ca-EX was most notably sustained when compared to other groups. Enzymatic degradation by chondroitinase ABC of CS, CS-Ca and CS-Ca-EX exhibited a similar degradation mechanism and GPC revealed the dissolution rate of CS from the three matrix types was, in decreasing order: CS, CS-Ca, CS-Ca-EX. The synergy of the anti-inflammatory activity of diclofenac sodium in CS-based complexes was evaluated using the carrageenan-induced edema rat test. The percentage of swelling was lower for all experimental groups as compared to the control, untreated group. The anti-inflammatory activity of diclofenac in the CS matrix gradually increased up to 9 h but CS-Ca or CS-Ca-EX matrices showed less potency than the CS matrix in reducing inflammation.
authors.affiliation: College of Life Science, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC.
authors.forename: Ming-Fung
authors.initials: MF
authors.lastname: Tsai
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Chiang
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Wang
authors.forename: Gao-Wei
authors.initials: GW
authors.lastname: Huang
authors.forename: Pao-Chu
authors.initials: PC
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002118:Calcium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004008:Diclofenac; D002809:Chondroitin Sulfates; D002118:Calcium