Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence.

Autor: Al Subeh ZY; Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States., Chu NQ; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, United States., Korunes-Miller JT; Department of Biomedical Engineering, Boston University, Boston, MA 02215, United States., Tsai LL; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, United States., Graf TN; Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States., Hung YP; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, United States., Pearce CJ; Mycosynthetix, Inc., Hillsborough, NC 27278, United States., Grinstaff MW; Department of Biomedical Engineering, Boston University, Boston, MA 02215, United States; Department of Chemistry, Boston University, Boston, MA 02215, United States., Colby AH; Department of Biomedical Engineering, Boston University, Boston, MA 02215, United States; Ionic Pharmaceuticals, LLC, Brookline, MA 02445, United States. Electronic address: acolby@bu.edu., Colson YL; Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, United States. Electronic address: ycolson@mgh.harvard.edu., Oberlies NH; Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States. Electronic address: nicholas_oberlies@uncg.edu.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2021 Mar 10; Vol. 331, pp. 260-269. Date of Electronic Publication: 2021 Jan 21.
DOI: 10.1016/j.jconrel.2021.01.026
Abstrakt: 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.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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