Encapsulated Carbenoxolone Reduces Lung Metastases

Area of Science:

• Pharmacology
• Oncology
• Drug Delivery Systems

Background:

• Carbenoxolone is an anti-inflammatory compound derived from licorice.
• Previous studies demonstrated carbenoxolone's efficacy in reducing lung metastasis via HMGB1 antagonism.
• Systemic administration of carbenoxolone can lead to adverse side effects due to widespread exposure.

Purpose of the Study:

• To develop a poly(lactic-co-glycolic acid) (PLGA) slow-release system for pulmonary delivery of carbenoxolone.
• To enhance carbenoxolone's activity and lung localization.
• To reduce systemic exposure and potential adverse effects of carbenoxolone.

Main Methods:

• Development of PLGA nanoparticles for carbenoxolone pulmonary delivery.
• In-vitro validation of drug activity using an anoikis assay.
• Evaluation of both systemic and intranasal carbenoxolone administration in a murine lung colonization model.
• Assessment of metastatic burden in lung tissue.

Main Results:

• The PLGA slow-release system maintained carbenoxolone activity in-vitro.
• Both systemic and intranasal carbenoxolone administration significantly reduced lung metastasis in mice.
• A single intranasal dose of carbenoxolone nanoparticles showed comparable efficacy to a 10-fold higher dose of free carbenoxolone administered over four weeks.
• Significant decrease in metastatic burden observed in lung tissue.

Conclusions:

• Pulmonary delivery of carbenoxolone using PLGA nanoparticles enhances anti-cancer activity.
• This approach allows for reduced dosage, improving therapeutic outcomes and minimizing side effects.
• The developed system offers a promising strategy for potentiating carbenoxolone's anti-metastatic effects in lung cancer.