Intranasal delivery of liposomal indole-3-carbinol improves its pulmonary bioavailability

Area of Science:

• Oncology
• Pharmacology
• Drug Delivery

Background:

• Indole-3-carbinol (I3C), found in Brassica vegetables, shows preclinical anticancer activity against lung cancer.
• Clinical efficacy of I3C is limited by poor oral bioavailability.
• Intranasal drug delivery can enhance pulmonary drug accumulation.

Purpose of the Study:

• To develop a liposomal formulation of I3C for intranasal administration.
• To evaluate the lung delivery and chemopreventive potential of liposomal I3C in a mouse model.
• To assess the impact of intranasal liposomal I3C on carcinogen-induced DNA adducts and detoxification enzymes.

Main Methods:

• Development of liposomal Indole-3-carbinol (I3C) formulation.
• Intranasal and oral administration of I3C in a mouse model exposed to the carcinogen 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK).
• Quantification of lung I3C exposure, DNA adduct levels, and CYP1A1 enzyme expression.

Main Results:

• Intranasal administration of liposomal I3C resulted in approximately 100-fold higher lung exposure compared to oral administration.
• Liposomal I3C delivered intranasally significantly reduced NNK-induced DNA adduct formation by 37% (p<0.05).
• Intranasal liposomal I3C treatment increased CYP1A1 expression 10-fold, indicating enhanced carcinogen metabolism.

Conclusions:

• Intranasal delivery of liposomal I3C significantly enhances lung drug exposure and bioavailability.
• This formulation demonstrates potent chemopreventive effects against tobacco smoke-induced lung carcinogenesis.
• Intranasal liposomal I3C represents a promising strategy to improve I3C efficacy for lung cancer prevention.