期刊
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
卷 12, 期 4, 页码 816-825出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s13346-021-00983-w
关键词
HIV; Intravaginal ring; pH-responsive polymer; Anti-CCR5 siRNA; Solid lipid nanoparticles
资金
- Canadian Institutes of Health Research [PJT166153]
- Natural Sciences and Engineering Research Council of Canada [RGPIN-20156-06008]
Vaginal drug delivery is a promising strategy for the prevention of sexually transmitted infections, with advantages such as improved therapeutic efficacy and reduced drug resistance. The developed IVR system can continuously release drugs and nanoparticles in a smart manner, showing positive effects in preventing infections.
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 mu g/mL. In the presence of vaginal fluid simulant plus seminal fluid simulant, over 12 x 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.
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