title: Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium-Loaded Alginate Microspheres.
abstract: The aims of this study were to prepare fine intra-articular-administrated chitosan thermosensitive hydrogels combined with alginate microspheres and to investigate the possibility of those hydrogels as a drug delivery system for promoting the anti-inflammation effect. Diclofenac sodium containing alginate microspheres was prepared by a modified emulsification and/or gelation method and then dispersed into injectable thermosensitive hydrogels, consisting of chitosan and β-glycerophosphate. The final combined hydrogels were evaluated in terms of their morphology properties, rheological properties, in vitro drug release, and in vivo biocompatibility and pharmacodynamics behaviors. The optimized formulation exhibited sol-gel transition at 31.72 ± 0.42°C and quickly turned into gel within 5 min, with sustained drug release characteristics followed Ritger-Peppas equation, which could prolong the in vitro drug release to 5 days. In addition, the anti-inflammation efficacy of the combined hydrogels in rabbits with experimental rheumatoid arthritis was higher than that of drug solution and pure chitosan hydrogels. Those results demonstrated that these combined hydrogels could become a potential drug delivery system for improving the therapeutic effect of diclofenac sodium and suggested an important technology platform for intra-articular administration.
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Xiaole
authors: X
authors: Qi
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Xiaoxue
authors: X
authors: Qin
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Rong
authors: R
authors: Yang
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Jiayi
authors: J
authors: Qin
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Wenyan
authors: W
authors: Li
authors: The Second Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, China.
authors: Kun
authors: K
authors: Luan
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: zhenghongwu66@cpu.edu.cn.
authors: Zhenghong
authors: Z
authors: Wu
authors: Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: songli1973@163.com.
authors: Li
authors: L
authors: Song
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D001169:Arthritis, Experimental / Q000188:drug therapy*; D048271:Chitosan / Q000737:chemistry*; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020100:Hydrogels; D007270:Injections, Intra-Articular; D008297:Male; D008863:Microspheres; D010316:Particle Size; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012212:Rheology; D013696:Temperature
chemical_list: D000464:Alginates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D006603:Hexuronic Acids; D020100:Hydrogels; D004008:Diclofenac; D020723:Glucuronic Acid; D048271:Chitosan
keywords: chitosan; controlled release; drug delivery systems; hydrogels; microspheres