Encapsulated Carbenoxolone Reduces Lung Metastases

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.

Nanoencapsulation of Pomegranate Extract to Increase Stability and Potential Dermatological Protection

“…Table 2 shows DLS analysis performed in a similar way to that previously reported [ 38 , 39 , 40 ]. The CI-vesicles had an average hydrodynamic diameter around 620.7 nm, which increased when PG-E was encapsulated in CI-vesicles (797.5 nm).…”

“…Dynamic light scattering (DLS) was used to detect particle size, zeta potential, and polydispersity index at a temperature of 20 °C using a Zetasizer Nano (Malvern Instruments, Malvern, UK) in a similar way as previously was reported [ 38 , 39 , 40 ]. Transmission electron microscopy (TEM) was performed as described previously [ 41 ].…”

Liquorice for pain?

“…According to one author, when treating gastrointestinal inflammation with carbenoxolone 4 , the common dosage is ‘100 mg for 1 week, three times a week, followed by a reduction to 50 mg every other day, to prevent potential side effects such as sodium retention, hypokalaemia, increased blood pressure and edema’. 78 …”

“…According to one author, when treating gastrointestinal inflammation with carbenoxolone 4, the common dosage is '100 mg for 1 week, three times a week, followed by a reduction to 50 mg every other day, to prevent potential side effects such as sodium retention, hypokalaemia, increased blood pressure and edema'. 78 Both GLA 1 and GRA 3 exhibit antithrombotic properties, inhibiting coagulation factor Xa and thrombin. A case of haemorrhagic stroke and cerebral microbleeds attributed to high intake of liquorice root supplement has been reported.…”

Carbenoxolone Ameliorates Allergic Airway Inflammation through NF-κB/NLRP3 Pathway in Mice

“…1); it has anti-inflammatory, -viral, -tumor, -bacterial, -fibrosis properties and neuroprotective activities amongst other extensive pharmacological activities. [11][12][13][14][15][16] It has been reported that CBX administration decreased lung inflammation in rats with pulmonary hypertension by increasing an anti-inflammatory cytokine, IL-10; decreasing tumor necrosis factor (TNF)-α, IL-1β, IL-6 and monocyte infiltration; and reducing the number of CD3 + and CD4 + T cells in lung tissues. 11) Another study indicated that CBX significantly inhibits NLRP3 activation and proinflammatory cytokine production thereby alleviating renal function and pathological damage in sepsis-induced acute kidney injury.…”