title: In vivo anti-apoptosis activity of novel berberine-loaded chitosan nanoparticles effectively ameliorates osteoarthritis.
abstract: Berberine chloride (BBR) is an isoquinoline alkaloid that possesses promising protective efficacies against osteoarthritis (OA). Nevertheless, the therapeutic agent of this substance in OA is limited by its poor aqueous solubility, low bioavailability and short biological half-life. In this study, chitosan (CS)-based nanoparticles were prepared for the sustained release of BBR. Novel BBR-loaded chitosan nanoparticles (CNs) were successfully synthesized by the ionic cross-linking method. BBR-loaded CNs were spherical and homogeneous in shape. Moreover, they exhibited good stability and had ideal releasing profile in vitro. After intra-articular injection of BBR-loaded CNs, the level of BBR in rat plasma decreased and the retention time in synovial fluid increased compared with free BBR solution. In vivo evaluation of BBR-loaded CNs further showed higher anti-apoptosis activity in the treatment of OA compared with BBR solution at equivalent concentration. This result was evidenced by the changes of gross morphology and histological analyses in rat articular cartilage, TUNEL assay, quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. Given these results, BBR-loaded CNs are potential therapeutic agents for OA.
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China. Electronic address: liusqrm@163.com.
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Orthopedics, Central Laboratory, Renmin Hospital, Wuhan University, Wuhan 430060, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000473:pathology; D048271:Chitosan / Q000737:chemistry; D019902:Chondrocytes / Q000187:drug effects; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004355:Drug Stability; D007270:Injections, Intra-Articular; D007596:Joints / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D016207:Cytokines; D001599:Berberine; D048271:Chitosan
keywords: Berberine; Chitosan; Drug release; Nanoparticles; Osteoarthritis