Development of an intravaginal ring for the topical delivery of Aurora kinase A inhibitor, MLN8237.
Administration, Intravaginal
Administration, Topical
Animals
Aurora Kinase A
/ antagonists & inhibitors
Azepines
/ administration & dosage
Female
Humans
Mice
Protein Kinase Inhibitors
/ pharmacology
Pyrimidines
/ administration & dosage
Tumor Cells, Cultured
Uterine Cervical Neoplasms
/ drug therapy
Xenograft Model Antitumor Assays
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
09
2019
accepted:
12
11
2019
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
26
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31774882
doi: 10.1371/journal.pone.0225774
pii: PONE-D-19-24851
pmc: PMC6880999
doi:
Substances chimiques
Azepines
0
MLN 8237
0
Protein Kinase Inhibitors
0
Pyrimidines
0
AURKA protein, human
EC 2.7.11.1
Aurora Kinase A
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0225774Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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