title: A novel melphalan polymeric prodrug: preparation and property study.
abstract: The clinical application of melphalan (Me), an anticancer drug for the treatment of hematologic malignancies, has been limited due to its poor water solubility, rapid elimination and lack of target specificity. To solve these problems, O,N-carboxymethyl chitosan-peptide-melphalan conjugates were synthesized and characterized. All polymeric prodrugs showed satisfactory water solubility. It was found that the molecular weight of O,N-carboxymethyl chitosan (O,N-CMCS) and the peptide spacer played a crucial role in controlling the drug content, diameter and drug release properties of O,N-carboxymethyl chitosan-peptide-melphalan conjugates. The studies of in vitro drug release and cell cytotoxicity by MTT assay revealed that, employing the polymeric conjugation strategy and using the peptides glycylglycine (Gly-Gly) as a spacer, the conjugates have good cathepsin X-sensitivity and lower toxicity and the drug release behavior improved remarkably. In conclusion, O,N-carboxymethyl chitosan-peptide-melphalan conjugates could be promising prodrugs for anticancer application.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China; Engineering Technology Center of Hubei traditional Chinese Medicine Preparation, Wuhan University of Technology, Wuhan 430070, PR China. Electronic address: whulb@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China; Engineering Technology Center of Hubei traditional Chinese Medicine Preparation, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China; Engineering Technology Center of Hubei traditional Chinese Medicine Preparation, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Peihu
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China; Engineering Technology Center of Hubei traditional Chinese Medicine Preparation, Wuhan University of Technology, Wuhan 430070, PR China. Electronic address: whutlvb@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China; Engineering Technology Center of Hubei traditional Chinese Medicine Preparation, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Haixing
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada T6G 2P5.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Yiceng
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Xueqiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical Engineering, Wuhan University of Technology, Wuhan 430070, PR China; Engineering Technology Center of Hubei traditional Chinese Medicine Preparation, Wuhan University of Technology, Wuhan 430070, PR China.
authors.forename: Fuliang
authors.initials: F
authors.lastname: Xiong
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006033:Glycylglycine / Q000737:chemistry; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D009101:Multiple Myeloma / Q000188:drug therapy; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D011355:Prodrugs; D006033:Glycylglycine; C077199:O,N-carboxymethylchitosan; D048271:Chitosan; D008558:Melphalan
keywords: Carboxymethyl chitosan; Cathepsin X; Melphalan; Nanoparticles