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The interstitial space, a widespread fluid-filled compartment throughout the body, is related to many pathophysiological alterations and diseases, attracting increasing attention. The vital role of interstitial space in malaria infection and treatment has been neglected current research efforts. We confirmed the reinfection capacity of parasites sequestrated in interstitial space, which replenish the mechanism of recurrence. Malaria parasite-infected mice were treated with artemisinin-loaded liposomes through the interstitial space and exhibited a better therapeutic response. Notably, compared with oral administration, interstitial administration showed an unexpectedly high activation and recruitment of immune cells, and resulted in better clearance of sequestered parasites from organs, and enhanced pathological recovery. The interstitial route of administration prolongs the blood circulation time of artemisinin and increases its plasma concentration, and may compensate for the inefficiency of oral administration and the nanotoxicity of intravenous administration, providing a potential strategy for infectious disease therapy.


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Neglected interstitial space in malaria recurrence and treatment

Show Author's information Qiang Zhang1,2Zhuo Ao1,2( )Nan Hu1,3Yuting Zhu1Fulong Liao1,4Dong Han1,2( )
CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
University of Chinese Academy of Sciences, Beijing 100049, China
Department of Traditional Chinese Medicine, Chengde Medical University, Chengde 066000, China
Artemisinin Research Center and the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100049, China

Abstract

The interstitial space, a widespread fluid-filled compartment throughout the body, is related to many pathophysiological alterations and diseases, attracting increasing attention. The vital role of interstitial space in malaria infection and treatment has been neglected current research efforts. We confirmed the reinfection capacity of parasites sequestrated in interstitial space, which replenish the mechanism of recurrence. Malaria parasite-infected mice were treated with artemisinin-loaded liposomes through the interstitial space and exhibited a better therapeutic response. Notably, compared with oral administration, interstitial administration showed an unexpectedly high activation and recruitment of immune cells, and resulted in better clearance of sequestered parasites from organs, and enhanced pathological recovery. The interstitial route of administration prolongs the blood circulation time of artemisinin and increases its plasma concentration, and may compensate for the inefficiency of oral administration and the nanotoxicity of intravenous administration, providing a potential strategy for infectious disease therapy.

Keywords: treatment, infection, interstitial space, malaria, recurrence

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Publication history
Copyright
Acknowledgements

Publication history

Received: 14 May 2020
Revised: 15 June 2020
Accepted: 19 June 2020
Published: 05 October 2020
Issue date: October 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81641002, 81841001 and 31971245), and Key Research Program of Frontier Sciences of CAS (No. ZDBS-LY-SLH036).

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