title: Extracorporeal delivery of a therapeutic enzyme.
abstract: To remove circulating harmful small biochemical(s)/substrates causing/deteriorating certain chronic disease, therapeutic enzyme(s) delivered via vein injection/infusion suffer(s) from immunoresponse after repeated administration at proper intervals for a long time and short half-lives since delivery. Accordingly, a novel, generally-applicable extracorporeal delivery of a therapeutic enzyme is proposed, by refitting a conventional hemodialysis device bearing a dialyzer, two pumps and connecting tubes, to build a routine extracorporeal blood circuit but a minimal dialysate circuit closed to circulate the therapeutic enzyme in dialysate. A special quantitative index was derived to reflect pharmacological action and thus pharmacodynamics of the delivered enzyme. With hyperuricemic blood in vitro and hyperuricemic geese, a native uricase via extracorporeal delivery was active in the dialysate for periods much longer than that in vivo through vein injection, and exhibited the expected pharmacodynamics to remove uric acid in hyperuricemic blood in vitro and multiple forms of uric acid in hyperuricemic geese. Therefore, the extracorporeal delivery approach of therapeutic enzymes was effective to remove unwanted circulating small biochemical(s)/substrates, and was expected to avoid immunogenicity problems of therapeutic enzymes after repeated administration at proper intervals for a long time due to no contacts with macromolecules and cells in the body.
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Urology, the First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Chongqing 400016, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Pu
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Liu
authors.affiliation: Molecular Modeling and Biopharmaceutical Center and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liao
mesh_terms: D000818:Animals; D015314:Dialysis Solutions / Q000737:chemistry*; D015199:Extracorporeal Membrane Oxygenation; D005777:Geese; D033461:Hyperuricemia / Q000097:blood* / Q000188:drug therapy*; D006435:Renal Dialysis / Q000295:instrumentation*; D014503:Urate Oxidase / Q000008:administration & dosage*; D014527:Uric Acid / Q000097:blood*
chemical_list: D015314:Dialysis Solutions; D014527:Uric Acid; D014503:Urate Oxidase