Designing a new vaginal prophylaxis for the release of biocompatible polymeric virucides

预防性传播病毒感染，例如人类免疫缺陷病毒（艾滋病毒）、单纯疱疹病毒-2 （HSV-2）和人类乳头瘤病毒（HPV），在全球都很重要。这些病毒可能具有威胁生命和/或改变生命的影响，而且许多病毒目前无法治疗。预防而不是治疗是处理性传播病毒感染的最佳方法。在有疫苗的地方，感染率可以大大降低。对于那些没有疫苗的病毒，需要通过其他手段进行预防。对于性传播感染，经常考虑但尚未成功实施的一种方法是使用阴道插入物预防性地释放抗病毒药物。目前最先进的抗hiv预防方法是阴道环插入，释放一种抗逆转录病毒（ARV）药物，这种药物在三期试验中只取得了有限的成功。这些抗病毒药物仅在感染后有效，具有固有毒性并导致病毒产生耐药性，这引起了人们对长期预防使用可能导致耐药病毒株的担忧。通过使用“接触即杀”抗病毒聚合物（Polycides）（最近由琼斯实验室开发），将有可能用一种全新的方法解决传播问题。作为一种预防措施，我们的多杀菌剂突破将在感染发生之前发挥作用，这意味着没有机会产生耐药性。本项目将重点设计一种新的基于水凝胶的多杀剂长期递送系统，研究其释放谱和体外研究，以显示细胞免受病毒感染的保护。

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.