Extracorporeal Delivery of a Therapeutic Enzyme

Authors

Chun Zhang, Chongqing Medical University, China
Jun Pu, Chongqing Medical University, China
Xiaolan Yang, Chongqing Medical University, China
Tao Feng, Chongqing Medical University, China
Fang Liu, Chongqing Medical University, China
Deqiang Wang, Chongqing Medical University, China
Xiaolei Hu, Chongqing Medical University, China
Ang Gao, Chongqing Medical University, China
Hongbo Liu, Chongqing Medical University, China
Chang-Guo Zhan, University of KentuckyFollow
Fei Liao, Chongqing Medical University, China

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.

Document Type

Article

Publication Date

8-1-2016

Notes/Citation Information

Published in Scientific Reports, v. 6, article no. 30888, p. 1-8.

© The Author(s) 2016

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Digital Object Identifier (DOI)

https://doi.org/10.1038/srep30888

Funding Information

The work was supported by National Natural Science Foundation of China (nos 30672139, 21402108 and 31570862), the Sciences and Technology Commission of Yuzhong District of Chongqing (no. 20130135), the Education Ministry of China (no. 20125503110007) and Chongqing Sciences and Technology Commission (CSTC2011BA5039).

Repository Citation

Zhang, Chun; Pu, Jun; Yang, Xiaolan; Feng, Tao; Liu, Fang; Wang, Deqiang; Hu, Xiaolei; Gao, Ang; Liu, Hongbo; Zhan, Chang-Guo; and Liao, Fei, "Extracorporeal Delivery of a Therapeutic Enzyme" (2016). Molecular Modeling and Biopharmaceutical Center Faculty Publications. 5.
https://uknowledge.uky.edu/mmbc_facpub/5