Aim:
In our laboratory, we have recently identified inhibiting Aurora A kinase as a selective approach to treat HPV-driven malignancies like cervical cancer, using Alisertib (MLN8237). However, Phase 1/2/3 clinical trials for oral Alisertib showed serious side effects related to the systemic delivery used.
As cervical cancer is localised in the early stages, localised delivery is feasible. This research focuses on designing a novel approach for topically targeting cervical cancer using Alisertib-loaded intra-vaginal rings and tests them in-vitro and in-vivo.
Methodology:
Matrix-type silicone intra-vaginal rings were designed, manufactured and optimised. Pharmacokinetics were tested in-vitro by incubating the rings under sink conditions in simulated vaginal fluid and safety was evaluated in-vivo in mice by implanting the rings for one week and then sectioning the vaginal tract to investigate for any indications of inflammation.
Results:
The silicone rings maintained continuous release of Alisertib over three weeks in the in vitro studies and exhibited root time kinetics. Mice vaginal tract sectioning showed no indication of inflammation related to the topical application of the drug over one week.
Conclusion:
Localising this novel approach will aid in reducing the required drug dose, avoiding the first pass metabolism, and reducing/avoiding the systemic side effects of the drug. Moreover, due to the direct contact between the delivery system and the surface of the malignancy, we presume that it will result in a significant improvement in therapy outcomes. This study provides an exciting opportunity to advance our knowledge of localising the treatment of cervical cancer.