Thermogelling materials for the improved vaginal retention of bioactives (360G-Wellcome-207201_Z_17_Z)

The transmission of HIV via the vaginal route can be hindered by the intravaginal administration of microbicides, as demonstrated by the CAPRISSA004 trial. Whilst there are promising ongoing investigations of this pre-exposure prophylaxis using intravaginal rings, there is a need for single-use products, such as vaginal gels, which limits the exposure to drug. Gels are poorly retained in the vagina, which reduces patient compliance and has led to the failure of a clinical trial (FACTS001). One method to improve retention is the use of "thermogelling" materials, which drastically increase in viscosity upon warming in the vagina. There are, however, a limited number of commercially available thermogelling polymers, and many materials show toxicity and low mechanical strength. Thus, it is desirable to develop novel thermogelling materials from biocompatible polymers, which would offer new platforms for the intravaginal delivery of drugs. This project aims to produce novel thermogelling materials using a hitherto poorly-explored temperature-responsive polymer, poly(N-vinylcaprolactam) (PNVCL). The student will aim to synthesise poly(ethylene glycol) (PEG) macroinitiators, from which PNVCL may be grown to yield PNVCL - PEG - PNVCL block copolymers, which are expected to posses thermogelling behaviour. This behaviour will then be explored using rheometry.