Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence.
Cancer recurrence
Eupenifeldin
Local drug delivery
Lung cancer
Polymer
Prolonged-release
Surgical buttress
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 03 2021
10 03 2021
Historique:
received:
02
11
2020
revised:
15
01
2021
accepted:
16
01
2021
pubmed:
24
1
2021
medline:
8
7
2021
entrez:
23
1
2021
Statut:
ppublish
Résumé
Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung cancer treatment with the potential for improved efficacy with reduced systemic toxicity. Here, we describe the development of a chemotherapy-loaded polymer buttress, to be implanted along the surgical margin at the time of tumor resection, for achieving local and prolonged release of a new anticancer agent, eupenifeldin. We prepared five different formulations of buttresses with varying amounts of eupenifeldin, and additional external empty polymer coating layers (or thicknesses) to modulate drug release. The in vitro eupenifeldin release profile depends on the number of external coating layers with the formulation of the greatest thickness demonstrating a prolonged release approaching 90 days. Similarly, the long-term cytotoxicity of eupenifeldin-loaded buttress formulations against murine Lewis lung carcinoma (LLC) and human lung carcinoma (A549) cell lines mirrors the eupenifeldin release profiles and shows a prolonged cytotoxic effect. Eupenifeldin-loaded buttresses significantly decrease local tumor recurrence in vivo and increase disease-free survival in a lung cancer resection model.
Identifiants
pubmed: 33484778
pii: S0168-3659(21)00035-3
doi: 10.1016/j.jconrel.2021.01.026
pmc: PMC7946725
mid: NIHMS1665361
pii:
doi:
Substances chimiques
Polymers
0
eupenifeldin
151803-45-1
Tropolone
7L6DL16P1T
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
260-269Subventions
Organisme : NIBIB NIH HHS
ID : R01 EB017722
Pays : United States
Organisme : NCI NIH HHS
ID : R43 CA224739
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA125066
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA232708
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227433
Pays : United States
Organisme : NCI NIH HHS
ID : R44 CA189215
Pays : United States
Organisme : NCI NIH HHS
ID : R43 CA213538
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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