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.
Highlights
Lung cancer is one of the deadliest diseases
To evaluate the effect of carbenoxolone loaded particles, and to confirm the formulation in its particulate form, we examined the level of resistance to apoptosis of non-adherent activity of the formulation in its particulate form, we examined the level of resistance to apoptosis of Lewis lung carcinoma (LLC) cells treated with drug-loaded particles for 72 h, by detecting cell viability on a non-adherent non-adherent
In a recently published study, we showed that carbenoxolone possesses anti-cancer properties mediated by its antagonistic effect on high mobility group box 1 (HMGB1), as demonstrated in mice that were pre-treated with the drug [8]
Summary
Lung cancer is one of the deadliest diseases. This is primarily due to the late diagnosis, which results from a lack of symptoms in the early stages, and which promotes high mortality rates [1,2,3]. Even among patients diagnosed at an early stage, metastases frequently develop, and therapeutic options are, rather limited [4,5]. In addition to the ongoing efforts for early lung cancer diagnosis, metastasis prevention is of great importance. Patients diagnosed with early-stage lung cancer, or those with primary tumors that are known to be susceptible to developing lung metastases could potentially benefit from such therapy, which could prevent further progression of the disease
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