title: Chitosan-modified lipid nanovesicles for efficient systemic delivery of l-asparaginase.
abstract: The goal of this study was to evaluate the enhanced catalytic activity, increased stability, in vitro anti-cancer effects on H446 cells and in vivo bioavailability of novel enzyme delivery nanovesicles (l-asparaginase containing chitosan modified lipid nanovesicles, ACLNs) when administered intravenously. It was the first time for the chitosan-modified lipid nanovesicles to be fabricated to deliver l-asparaginase (ASP, a therapeutic enzyme) efficiently. It was indicated that ACLNs markedly increased the enzymatic activity, improved the temperature/acid-base/proteolytic stabilities and favorably changed the in vivo kinetic characteristics. Moreover, ACLNs exhibited higher anti-lung-cancer activity than free ASP. The possible existence status of ASP in ACLNs and the fluorescence changes of ACLNs reflecting the conformational changes after heat treatment were preliminary explored. ACLNs might be novel promising nanovesicles for effective systemic delivery of therapeutic enzyme ASP.
authors.affiliation: Chongqing Research Center for PharmaceuticalEngineering, Chongqing Medical University, Chongqing, China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Wan
authors.affiliation: Chongqing Research Center for PharmaceuticalEngineering, Chongqing Medical University, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Chongqing Research Center for PharmaceuticalEngineering, Chongqing Medical University, Chongqing, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Chongqing Research Center for PharmaceuticalEngineering, Chongqing Medical University, Chongqing, China.
authors.forename: Zijun
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Chongqing Research Center for PharmaceuticalEngineering, Chongqing Medical University, Chongqing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Chongqing Research Center for PharmaceuticalEngineering, Chongqing Medical University, Chongqing, China. Electronic address: zjqrae01@163.com.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D019540:Area Under Curve; D001215:Asparaginase / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D008055:Lipids; D048271:Chitosan; D001215:Asparaginase
keywords: Catalytic activity; Chitosan modified lipid nanovesicles; Systemic enzyme delivery; Therapeutic enzyme; l-Asparaginase