Improving maternal reproductive health, combating HIV/AIDS, and preventing sexually transmitted infections (STIs) are major global health priorities specifically highlighted under the UN Millennium Development Goals. Often, the risks associated with these clinical indications are inter-related. For example, genital HSV-2 infection in women is associated with a three-fold increased risk of HIV acquisition. Unfortunately, these individual health goals have not yet been achieved. A preferred strategy would involve a single pharmaceutical product/device that addresses at least two, and preferably three, of these clinical indications. A matrix-type VR, developed by the Queen’s University Belfast (QUB) and the International Partnership for Microbicides (IPM) and providing controlled release of the antiretroviral compound dapivirine (DAP), is presently being tested in a Phase III study as a potential microbicide for HIV prevention. Second generation VRs, comprising either two HIV microbicides (DAP and maraviroc, MVC) or a combination of DAP and levonorgestrel (LNG), are also in or about to enter early stage clinical development. The primary objective of this PhD project was to develop a multiple core, reservoir-type vaginal ring for delivery and maintenance of potentially clinically effective drug concentrations of anti-HIV drug dapivirine (DAP), progestin (levonorgestrel) and anti-HSV drug famciclovir (FMV). DAP-only and LNG-only vaginal rings have already been tested clinically, and there is much consensus on their clinical effective levels. Given than FMV has not previously been tested for vaginal administration, we developed different strategies to control and maximise the release of the drugs from the rings. In addition to FMV, two more experimental anti-HSV drugs pritelivir (PVR), its salt form pritelivir mesylate (PVR-M) and second drug north-methanocarbathymidine (N-MCT) have been tested for vaginal ring formulations in this research project.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:707805 |
| Date | January 2016 |
| Creators | Kumar, Sandeep |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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