Implant delivering hydroxychloroquine attenuates vaginal T lymphocyte activation and inflammation

J Control Release. 2018 May 10;277:102-113. doi: 10.1016/j.jconrel.2018.03.010. Epub 2018 Mar 13.

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.

Keywords: Antiviral; Drug release; HIV/AIDS; Hydroxychloroquine; Intravaginal ring; Polymeric drug carrier.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Animals
  • Drug Delivery Systems / methods*
  • Drug Implants / administration & dosage*
  • Drug Implants / metabolism
  • Female
  • Hydroxychloroquine / administration & dosage*
  • Hydroxychloroquine / metabolism
  • Inflammation / diagnostic imaging
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Rabbits
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Vagina / diagnostic imaging
  • Vagina / drug effects*
  • Vagina / metabolism

Substances

  • Drug Implants
  • Hydroxychloroquine