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Implant delivering hydroxychloroquine attenuates vaginal T lymphocyte activation and inflammation

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Chen et al 2018 Accepted Manuscript.pdf (20.51 MB)

Date

2018-05-10

Authors

Chen, Yufei
Traore, Yannick L.
Yang, Sidi
Lajoie, Julie
Fowke, Keith R.
Rickey, Daniel W.
Ho, Emmanuel A.

Journal Title

Journal ISSN

Volume Title

Publisher

Elsevier

Abstract

Evidence suggests that women who are naturally resistant to HIV infection exhibit low baseline immune activation at the female genital tract (FGT). This “immune quiescent” state is associated with lower expression of T-cell activation markers, reduced levels of gene transcription and pro-inflammatory cytokine or chemokine production involved in HIV infection while maintaining an intact immune response against pathogens. Therefore, if this unique immune quiescent state can be pharmacologically induced locally, it will provide an excellent women-oriented strategy against HIV infection To our knowledge, this is the first research article evaluating in vivo, an innovative trackable implant that can provide controlled delivery of hydroxychloroquine (HCQ) to successfully attenuate vaginal T lymphocyte activation and inflammation in a rabbit model as a potential strategy to induce an “immune quiescent” state within the FGT for the prevention of HIV infection. This biocompatible implant can deliver HCQ above therapeutic concentrations in a controlled manner, reduce submucosal immune cell recruitment, improve mucosal epithelium integrity, decrease protein and gene expression of T-cell activation markers, and attenuate the induction of key pro-inflammatory mediators. Our results suggest that microbicides designed to maintain a low level of immune activation at the FGT may offer a promising new strategy for reducing HIV infection.

Description

The final publication is available at Elsevier via https://doi.org/10.1016/j.jconrel.2018.03.010 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

Antiviral, Drug release, HIV/AIDS, Hydroxychloroquine, Intravaginal ring, Polymeric drug carrier

LC Keywords

Citation

URI

https://doi.org/10.1016/j.jconrel.2018.03.010
 http://hdl.handle.net/10012/13258

Collections

Waterloo Research
Pharmacy