title: Nanocapsule assemblies as effective enzyme delivery systems against hyperuricemia.
abstract: The uricase nanocapsule assemblies (UNAs) were developed as effective delivery systems against hyperuricemia following parenteral enzyme therapy. UNAs were characterized in terms of micromorphology, size, catalytic activity, stability, and enzymatic kinetics. The pharmacokinetics/pharmacodynamics in rats after intravenous or subcutaneous injection was investigated. Immunogenicity, hemolysis and stimulation were determined. UNA was composed of many nanocapsules, and thus had higher loading efficiencies and stabilities than a single nanocapsule. The uricase molecules entrapped inside nanocapsules were separated from the circulating bloodstream to retain catalytic activities for a longer time than free uricase. UNAs increased the bioavailability and uric acid-lowering efficacy of uricase, while the immunogenicity and hemolysis rate of uricase were decreased. The superior properties of UNAs might be ascribed to the favorable conformational changes of uricase. Nanocapsule assemblies appeared to be able to deliver uricase effectively. This study also highlighted the importance of suitable systems for therapeutic enzyme delivery.
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Deng
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China. Electronic address: zjqrae01@163.com.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001682:Biological Availability; D006461:Hemolysis; D033461:Hyperuricemia / Q000188:drug therapy*; D053769:Nanocapsules / Q000008:administration & dosage*; D051381:Rats; D014503:Urate Oxidase / Q000008:administration & dosage*; D014527:Uric Acid
chemical_list: D053769:Nanocapsules; D014527:Uric Acid; D014503:Urate Oxidase
keywords: Enzymatic therapy; Enzyme delivery systems; Hyperuricemia; Nanocapsule assemblies; Uricase