title: Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer.
abstract: Cervical cancer is the third most prevalent cancer in women and disproportionately affects those in low resource settings due to limited programs for screening and prevention. In the developed world treatment for the disease in the non-metastasised state usually takes the form of surgical intervention and/or radiotherapy. In the developing world such techniques are less widely available. This paper describes the development of an intravaginal ring for the localised delivery of a chemotherapeutic drug to the cervix that has the potential to reduce the need for surgical intervention and will also provide a novel anti-cancer therapy for women in low resource settings. Disulfiram has demonstrated antineoplastic action against prostate, breast and lung cancer. Both PEVA and silicone elastomer were investigated for suitability as materials in the manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process of the silicone elastomer, therefore PEVA was chosen as the material to manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent content uniformity while the DSF remained stable throughout the manufacturing process. Furthermore, the rings provided diffusion controlled release of DSF at levels well in excess of the IC50 value for the HeLa cervical cancer cell line.
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University of Belfast, Belfast, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Boyd
authors.affiliation: Materials Research Institute, Athlone Institute of Technology, Westmeath, Ireland.
authors.forename: Ian
authors.initials: I
authors.lastname: Major
authors.affiliation: Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK. Electronic address: C.Mcconville@wlv.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: McConville
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D003274:Contraceptive Devices, Female / Q000639:trends; D004221:Disulfiram / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004221:Disulfiram
keywords: Cervical cancer; Controlled release; Disulfiram; Localised delivery; Sustained release; Vaginal ring