Implant delivering hydroxychloroquine attenuates vaginal T lymphocyte activation and inflammation

JOURNAL OF CONTROLLED RELEASE

卷:277

Article

Chen, Yufei^1,2  Traore, Yannick L.¹  Yang, Sidi¹  Lajoie, Julie³  Fowke, Keith R.^3,4,7  Rickey, Daniel W.^5,6  Ho, Emmanuel A.¹ 

[1] Univ Waterloo, Sch Pharm, Lab Drug Delivery & Biomat, 10A Victoria St S, Kitchener, ON N2G 1C5, Canada

[2] Univ Manitoba, Coll Pharm, Winnipeg, MB, Canada

[3] Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada

[4] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB, Canada

[5] Univ Manitoba, Dept Radiol, Winnipeg, MB, Canada

[6] Univ Manitoba, Dept Phys & Astron, Winnipeg, MB, Canada

[7] Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya

关键词: HIV/AIDS;    Hydroxychloroquine;    Antiviral;    Polymeric drug carrier;    Drug release;    Intravaginal ring;   

DOI  :  10.1016/j.jconrel.2018.03.010

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free