Segmented intravaginal ring for the combination delivery of hydroxychloroquine and anti-CCR5 siRNA nanoparticles as a potential strategy for preventing HIV infection
| Autor: | Emmanuel A. Ho, Yannick Leandre Traore, Yufei Chen, Fernanda Padilla |
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| Rok vydání: | 2021 |
| Předmět: |
T cell
Pharmaceutical Science HIV Infections Drug resistance Pharmacology 03 medical and health sciences 0302 clinical medicine Immune system Solid lipid nanoparticle medicine Humans 030212 general & internal medicine RNA Small Interfering 030304 developmental biology 0303 health sciences Gene knockdown business.industry Correction Hydroxychloroquine In vitro Administration Intravaginal medicine.anatomical_structure Drug delivery Nanoparticles Female business medicine.drug |
| Zdroj: | Drug Deliv Transl Res |
| ISSN: | 2190-3948 2190-393X |
| Popis: | Abstract Vaginal drug delivery has been shown to be a promising strategy for the prevention of sexually transmitted infections. Therapy delivered at the site of infection has many advantages including improved therapeutic efficacy, reduction in systemic toxicity, and reduced potential for development of drug resistance. We developed a “smart” combination intravaginal ring (IVR) that will (1) provide continuous release of hydroxychloroquine (HCQ) to induce T cell immune quiescence as the first-line of defense and (2) release nanoparticles containing anti-CCR5 siRNA only during sexual intercourse when triggered by the presence of seminal fluid as the second-line of defense. The IVR was capable of releasing HCQ over 25 days with a mean daily release of 31.17 ± 3.06 µg/mL. In the presence of vaginal fluid simulant plus seminal fluid simulant, over 12 × more nanoparticles (5.12 ± 0.9 mg) were released over a 4-h period in comparison to IVR segments that were incubated in the presence of vaginal fluid simulant alone (0.42 ± 0.19 mg). Anti-CCR5 siRNA nanoparticles were able to knockdown 83 ± 5.1% of CCR5 gene expression in vitro in the CD4+ T cell line Sup-T1. The IVR system also demonstrated to be non-cytotoxic to VK2/E6E7 vaginal epithelial cells. Graphical abstract |
| Databáze: | OpenAIRE |
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