Application deadline: 3rd March
Interviews to be held: 31 March 2021
The prevention of sexually transmitted viral infections such as, human immunodeficiency viruses (HIV), herpes simplex virus–2 (HSV-2) and human papilloma virus (HPV) for example, is important globally. These viruses can have life threatening and/or life altering effects and many are not currently treatable. Prevention rather than treatment is the best approach to dealing with sexually transmitted viral infections. Where vaccines are available, infection rates can be significantly reduced. For those viruses that have no vaccine, prevention via other means is necessary. One approach often considered, but not yet implemented successfully for sexually transmitted infections, is the use of vaginal inserts to release antivirals prophylactically. The current state-of-the-art anti-HIV prophylaxis is a vaginal ring insert that releases an anti-retroviral (ARV) drug, which has seen only limited success in Phase-III trials. These antivirals are only effective after infection, are inherently toxic and lead to viruses developing drug resistance, raising concerns that long-term prophylaxis use may lead to drug resistant viral strains.
Through the use of ‘kill on contact’ antiviral polymers (Polycides) (which have recently been developed in the Jones Lab) it will be possible to tackle the problem of transmission using an entirely new approach. As a prophylaxis our Polycides breakthrough will function before infection occurs meaning there is no opportunity for resistance to develop.
This project will focus on the design of a new hydrogel-based long-term delivery system for these polycides, the study of the release profiles and the in-vitro studies to show protection of cells from viral infection.
Main question to answered
Figure 1 – Overview of proposed route to creation and testing of polycide releasing vaginal ring insert
Can a hydrogel vaginal insert be synthesised that allows for long-term release of polycides leading to protection from sexually transmitted viral infections?
The project would focus on the development of a cross-linked polymeric hydrogel capable of controlled release of polycides. Typically hydrogels are used in the release of small molecule drugs and their release profiles are typically short. The release of the highly soluble and much larger polycides presents new challenges compared with small molecule drugs. Understanding the release profile is essential for drug delivery via a vaginal ring insert in order to be able to advise users of time between replacements.
The student will be required to synthesise and test, in a lab setting, several hydrogel compositions with dye labelled polycides. Regular discussion with the external advisor will allow for rapid identification of the most suitable hydrogel systems. Lab-based studies will allow for the ideal release rate profiles to be identified before moving to in-vitro testing, which will involve both toxicity testing and prevention of infection studies over a period of time. If successful protection of cells is achieved, tests with ex-vivo vaginal tissues will be performed. By the end of this project a vaginal ring insert will have been generated, ready for in-vivo testing.
PLACEMENT INFORMATION
Students please note this placement will be at the Stanford University
EPSRC Centre for Doctoral Training in Advanced Biomedical Materials
This project is part of the EPSRC Centre for Doctoral Training in Advanced Biomedical Materials. All available projects are listed here.
Find out how to apply, with full details on eligibility and funding here.
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