Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications.
Endometrial cancer
Everolimus
Poly(propylene fumarate)
Polymer-based intrauterine delivery
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
10 11 2021
10 11 2021
Historique:
received:
09
05
2021
revised:
22
09
2021
accepted:
07
10
2021
pubmed:
15
10
2021
medline:
15
12
2021
entrez:
14
10
2021
Statut:
ppublish
Résumé
Non-surgical treatment options for low-grade endometrial cancer and precancerous lesions are a critical unmet need for women who wish to preserve fertility or are unable to undergo hysterectomy. The PI3K/AKT/mTOR pathway is frequently activated in endometrial cancers and has been associated with resistance to endocrine therapy, making it a compelling target for early stage disease. Oral everolimus, an inhibitor against mTORC1, has shown clinical benefit in advanced or recurrent disease but has severe adverse effects that may lead to treatment interruption or dose reduction. To overcome this, we developed a polymer-based intrauterine delivery system to achieve persistent, local delivery of everolimus without systemic exposure. In vivo studies, using a rat model, showed that a poly(propylene fumarate)-based rod loaded with everolimus achieved everolimus delivery to the endometrium with levels similar to oral administration, but with limited systemic exposure and up to 84 days of release. Biological activity of everolimus delivered with this system was confirmed, measured by reduced lumen epithelial cell height and PI3K pathway biomarkers. This study shows a promising new delivery approach for anti-cancer drugs for non-surgical treatment of low-grade endometrial cancer.
Identifiants
pubmed: 34648891
pii: S0168-3659(21)00537-X
doi: 10.1016/j.jconrel.2021.10.008
pmc: PMC8650567
mid: NIHMS1750109
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Polymers
0
Everolimus
9HW64Q8G6G
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
521-530Subventions
Organisme : NCI NIH HHS
ID : T32 CA101642
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA056452
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA098258
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA142543
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB023833
Pays : United States
Organisme : NIDCR NIH HHS
ID : F31 DE027586
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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