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Enhanced nanoparticle uptake into virus infected cells: could nanoparticles be useful in antiviral therapy?

Abo-zeid, Yasmin; Urbanowicz, Richard A.; Thomson, Brian J.; Irving, William L.; Tarr, Alexander W.; Garnett, Martin C.

Authors

Yasmin Abo-zeid

Richard A. Urbanowicz

Brian J. Thomson

Martin C. Garnett



Abstract

Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threatening diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy. Nanoparticles (NP) can be effectively targeted to the liver, and therefore it could be used for improving therapy of hepatic virus infections including hepatitis B virus and hepatitis C virus (HCV). Many studies were performed to encapsulate antiviral agents into nano-delivery system to improve their pharmacokinetics parameters to have a better therapeutic efficacy with lower side effects. However, the effect of virus infection on the uptake of NP has not yet been studied in detail. The latter is a crucial area as modulation of endocytic uptake of nanoparticles could impact on reduce potential therapeutic usefulness of antiviral agents loaded into nano-delivery system. In this study, a fluorescently-labelled polymeric nanoparticle was prepared and used to track NP uptake into Huh7.5, human hepatoma cells transfected with replicating HCV genomes, compared with non-transfected cells as a model representing hepatocyte uptake. Confocal microscopy and flow cytometry of virus transfected Huh7.5 cells unexpectedly demonstrated two-fold increase in uptake of NP compared to non-transfected cells. Therefore, virus transfection enhanced NP uptake into Huh7.5 cells and NP could be considered as a promising delivery system for targeted treatment of hepatitis viruses.

Citation

Abo-zeid, Y., Urbanowicz, R. A., Thomson, B. J., Irving, W. L., Tarr, A. W., & Garnett, M. C. (2018). Enhanced nanoparticle uptake into virus infected cells: could nanoparticles be useful in antiviral therapy?. International Journal of Pharmaceutics, 547(1-2), https://doi.org/10.1016/j.ijpharm.2018.06.027

Journal Article Type Article
Acceptance Date Jun 9, 2018
Online Publication Date Jun 13, 2018
Publication Date Aug 25, 2018
Deposit Date Jun 20, 2018
Publicly Available Date Jun 14, 2019
Journal International Journal of Pharmaceutics
Print ISSN 0378-5173
Electronic ISSN 1873-3476
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 547
Issue 1-2
DOI https://doi.org/10.1016/j.ijpharm.2018.06.027
Keywords HCV infection; Polymer nanoparticles; Poly(glycerol adipate); Huh7.5 cells
Public URL http://eprints.nottingham.ac.uk/id/eprint/52524
Publisher URL http://dx.doi.org/10.1016/j.ijpharm.2018.06.027
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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