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Karsch-Bluman A, Avraham S, Assayag M, et al. Encapsulated Carbenoxolone Reduces Lung Metastases. Cancers (Basel). 2019;11(9)doi: 10.3390/cancers11091383.
Karsch-Bluman, A., Avraham, S., Assayag, M., Schwob, O., & Benny, O. (2019). Encapsulated Carbenoxolone Reduces Lung Metastases. Cancers, 11(9), . https://doi.org/10.3390/cancers11091383
Karsch-Bluman, Adi, et al. "Encapsulated Carbenoxolone Reduces Lung Metastases." Cancers vol. 11,9 (2019). doi: https://doi.org/10.3390/cancers11091383
Karsch-Bluman A, Avraham S, Assayag M, Schwob O, Benny O. Encapsulated Carbenoxolone Reduces Lung Metastases. Cancers (Basel). 2019 Sep 17;11(9). doi: 10.3390/cancers11091383. PMID: 31533288; PMCID: PMC6771083.
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Cancers (Basel). 2019 Sep 17;11(9). doi: 10.3390/cancers11091383.

Encapsulated Carbenoxolone Reduces Lung Metastases.

Cancers

Adi Karsch-Bluman, Shimrit Avraham, Miri Assayag, Ouri Schwob, Ofra Benny

Affiliations

  1. The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 9112102 Jerusalem, Israel. [email protected].
  2. Department of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron 1, 3535422 Haifa, Israel. [email protected].
  3. The Institute of Pulmonary Medicine at Hadassah-Hebrew University Medical Center, 9112102 Jerusalem, Israel. [email protected].
  4. The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 9112102 Jerusalem, Israel. [email protected].
  5. The Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 9112102 Jerusalem, Israel. [email protected].

PMID: 31533288 PMCID: PMC6771083 DOI: 10.3390/cancers11091383

Abstract

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.

Keywords: cancer; carbenoxolone; double emulsion; drug delivery; intranasal administration; lungs; metastases; particles

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