Long-acting drug delivery from intravaginal rings for treatment of cervical intraepithelial neoplasia

Building on our world-renowned expertise in vaginal drug delivery, the aim of this project is to develop a long-acting vaginal ring device for treatment of cervical intraepithelial neoplasia.
Cervical intraepithelial neoplasia (CIN) is the precursor of cervical cancer, the third most common cancer in women worldwide. In most patients, CIN is an asymptomatic condition that can regress to normal without treatment, or takes years to progress to invasive cancer. A strong correlation has been shown between CIN and infection with the human papillomavirus (HPV). The currently preferred treatment for high grade CIN is surgical excision, although this is commonly associated with adverse pregnancy outcomes and recurrence is not uncommon.
There are no medical therapies currently recommended to promote the clearance of HPV or cervical dysplasia. In particular, there is a need for non-invasive treatment modalities, targeting the source of the condition instead of the consequence, and through which recurrence rates and adverse effects are minimized. Several topical semi-solid pharmaceutical products are being considered for use in the treatment of CIN, containing either imiquimod (an immune response modifier) or 5-fluorouracil (an antineoplastic agent). For example, Rahangdale et al. have reported encouraging clinical data for treatment of CIN using a vaginally-administered cream containing 5-fluorouracil. Also, numerous studies have reported the potential for topical administration of imiquimod. The use of intravaginal therapies for treatment of CIN 2/3 merits further study, particularly given patient interest and potential efficacy in alternatives to traditional management of CIN.
In this project, for the first time, we will develop and test an intravaginal ring device – fabricated by injection molding technologies from either silicone elastomer of thermoplastic materials – for long-acting, user-friendly, treatment of CIN. Both single active and combination actives products will be tested, initially focusing on imiquimod and 5-fluorouracil. A wide range of methods and techniques will be applied during the development programme, including (i) ring manufacture, (ii) mechanical testing, (ii) in vitro release testing, (iv) thermal analysis testing, (v) drug content assay development, (vi) product stability testing, (vi) development of analytical methods, (vii) evaluation of potential animal models. The successful student will work as part of well-established and
supportive research team, with access to state-of-the-art equipment and laboratories.