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Encapsulated Carbenoxolone Reduces Lung Metastases
Carbenoxolone is an anti-inflammatory compound and a derivate of a natural substance from the licorice plant. We previously showed that carbenoxolone reduces the metastatic burden in the lungs of mice through its antagonistic effect on high mobility group box 1 (HMGB1). To further enhance carbenoxol...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771083/ https://www.ncbi.nlm.nih.gov/pubmed/31533288 http://dx.doi.org/10.3390/cancers11091383 |
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author | Karsch-Bluman, Adi Avraham, Shimrit Assayag, Miri Schwob, Ouri Benny, Ofra |
author_facet | Karsch-Bluman, Adi Avraham, Shimrit Assayag, Miri Schwob, Ouri Benny, Ofra |
author_sort | Karsch-Bluman, Adi |
collection | PubMed |
description | Carbenoxolone is an anti-inflammatory compound and a derivate of a natural substance from the licorice plant. We previously showed that carbenoxolone reduces the metastatic burden in the lungs of mice through its antagonistic effect on high mobility group box 1 (HMGB1). To further enhance carbenoxolone’s activity and localization in the lungs, thereby reducing the potential adverse side effects resulting from systemic exposure, we developed a poly(lactic-co-glycolic acid) (PLGA) slow-release system for pulmonary delivery which maintains drug activity in-vitro, as demonstrated in the anoikis assay. Both systemic and intranasal administrations of carbenoxolone effectively minimize metastatic formation in a lung colonization model in mice. Our results show a decrease in the metastatic burden in the lung tissue. Notably, the therapeutic effect of a single intranasal administration of 25 mg/kg carbenoxolone, in the form of drug-loaded particles, had a similar effect in reducing metastatic lesions in the lungs to that of a 10-fold dose of the free drug via intraperitoneal injections, three times per week over the course of four weeks. These data offer new means to potentiate the anti-cancer activity of carbenoxolone and simultaneously reduce the requirement for high dosage administration; the upshot substantially improves therapeutic effect and avoidance of side effects. |
format | Online Article Text |
id | pubmed-6771083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67710832019-10-30 Encapsulated Carbenoxolone Reduces Lung Metastases Karsch-Bluman, Adi Avraham, Shimrit Assayag, Miri Schwob, Ouri Benny, Ofra Cancers (Basel) Article Carbenoxolone is an anti-inflammatory compound and a derivate of a natural substance from the licorice plant. We previously showed that carbenoxolone reduces the metastatic burden in the lungs of mice through its antagonistic effect on high mobility group box 1 (HMGB1). To further enhance carbenoxolone’s activity and localization in the lungs, thereby reducing the potential adverse side effects resulting from systemic exposure, we developed a poly(lactic-co-glycolic acid) (PLGA) slow-release system for pulmonary delivery which maintains drug activity in-vitro, as demonstrated in the anoikis assay. Both systemic and intranasal administrations of carbenoxolone effectively minimize metastatic formation in a lung colonization model in mice. Our results show a decrease in the metastatic burden in the lung tissue. Notably, the therapeutic effect of a single intranasal administration of 25 mg/kg carbenoxolone, in the form of drug-loaded particles, had a similar effect in reducing metastatic lesions in the lungs to that of a 10-fold dose of the free drug via intraperitoneal injections, three times per week over the course of four weeks. These data offer new means to potentiate the anti-cancer activity of carbenoxolone and simultaneously reduce the requirement for high dosage administration; the upshot substantially improves therapeutic effect and avoidance of side effects. MDPI 2019-09-17 /pmc/articles/PMC6771083/ /pubmed/31533288 http://dx.doi.org/10.3390/cancers11091383 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Karsch-Bluman, Adi Avraham, Shimrit Assayag, Miri Schwob, Ouri Benny, Ofra Encapsulated Carbenoxolone Reduces Lung Metastases |
title | Encapsulated Carbenoxolone Reduces Lung Metastases |
title_full | Encapsulated Carbenoxolone Reduces Lung Metastases |
title_fullStr | Encapsulated Carbenoxolone Reduces Lung Metastases |
title_full_unstemmed | Encapsulated Carbenoxolone Reduces Lung Metastases |
title_short | Encapsulated Carbenoxolone Reduces Lung Metastases |
title_sort | encapsulated carbenoxolone reduces lung metastases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771083/ https://www.ncbi.nlm.nih.gov/pubmed/31533288 http://dx.doi.org/10.3390/cancers11091383 |
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