Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model.

Autor: Nief C; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Morhard R; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Chelales E; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Adrianzen Alvarez D; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Bourla Bs I; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Lam CT; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Sag AA; Department of Interventional Radiology, Duke University School of Medicine, Durham, North Carolina, United States of America., Crouch BT; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.; The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, North Carolina, United States of America., Mueller JL; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America., Katz D; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.; Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, United States of America., Dewhirst MW; Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina, United States of America., Everitt JI; Department of Pathology, Duke University, Durham, North Carolina, United States of America., Ramanujam N; Department of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.; Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, United States of America.; Duke Global Health Institute, Duke University, Durham, North Carolina, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Jan 28; Vol. 16 (1), pp. e0234535. Date of Electronic Publication: 2021 Jan 28 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0234535
Abstrakt: Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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