Development of an intravaginal ring for the topical delivery of Aurora kinase A inhibitor, MLN8237

Autoři: Yaman Tayyar aff001;  Ryan Shiels aff001;  Andrew C. Bulmer aff001;  Alfred K. Lam aff002;  Daniel Clarke aff001;  Adi Idris aff001;  Nigel A. McMillan aff001
Působiště autorů: School of Medical Science, Griffith University, Southport, Australia aff001;  Menzies Health Institute Queensland, Griffith University, Southport, Australia aff002
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225774


Human papilloma virus (HPV) is the main culprit in cervical cancers. Although the HPV vaccine is now available, the slow and gradual process for HPV cancers to form means little will change, even for vaccinated individuals. This warrants the development of new therapeutic strategies in both the newly diagnosed and recurrent patients. We have previously shown that Alisertib (MLN8237), an Aurora A kinase inhibitor, potently and selectively kills HPV-positive cervical cancer cells. However, Alisertib is known for its unfavorable side effects when administered systemically. A targeted delivery approach is therefore warranted. The topical delivery of drugs to the cervix for the treatment of cervical cancer is an underexplored area of research that has the potential to significantly improve therapeutic outcome. Here, we design a novel topical drug delivery system for localized delivery in the vaginal tract using intravaginal silicone rings loaded with Alisertib. We assessed the suitability of the drug for the application and delivery method and develop a high-performance liquid chromatography method, then show that the vaginal rings were effective at releasing Alisertib over an extended period of time. Furthermore, we showed that Alisertib-loaded vaginal rings did not induce overt inflammation in the mouse vaginal tract. Our work has major translational implications for the future development of vaginal ring devices for the topical treatment of cervical cancer.

Klíčová slova:

Cancer treatment – Cervical cancer – Drug delivery – High performance liquid chromatography – Human papillomavirus – Inflammation – Medical implants – Silicones


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2019 Číslo 11