title: Preparation, characterization, and in vitro efficacy of O-carboxymethyl chitosan conjugate of melphalan.
abstract: A series of melphalan-O-carboxymethyl chitosan (Mel-OCM-chitosan) conjugates with different spacers were prepared and structurally characterized. All conjugates showed satisfactory water-solubility (160-217 times of Mel solubility). In vitro drug release behaviors by both chemical and enzymatic hydrolysis were investigated. The prodrugs released Mel rapidly within papain and lysosomal enzymes of about 40-75%, while released only about 4-5% in buffer and plasma, which suggested that the conjugates have good plasma stability and the hydrolysis in both papain and lysosomes occurs mostly via enzymolysis. It was found that the spacers have important effect on the drug content, water solubility, drug release properties and cytotoxicity of Mel-OCM-chitosan conjugates. Cytotoxicity studies by MTT assay demonstrated that these conjugates had 52-70% of cytotoxicity against RPMI8226 cells in vitro as compared with free Mel, indicating the conjugates did not lose anti-cancer activity of Mel. Overall these studies indicated Mel-OCM-chitosan conjugates as potential prodrugs for cancer treatment.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Huang
authors.forename: Peihu
authors.initials: P
authors.lastname: Xu
authors.forename: Haixing
authors.initials: H
authors.lastname: Xu
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yin
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Xueqiong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006801:Humans; D008558:Melphalan / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D011355:Prodrugs / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011355:Prodrugs; C514968:carboxymethyl-chitosan; D014867:Water; D048271:Chitosan; D008558:Melphalan
keywords: Carboxymethyl chitosan; Melphalan; Polymeric prodrug