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

Abstract

Indole-3-carbinol (I3C), a constituent of commonly consumed Brassica vegetables, has been shown to have anticancer effects in a variety of preclinical models of lung cancer. However, it has shown only limited efficacy in clinical trials, likely due to its poor oral bioavailability. Intranasal administration of I3C has the potential to enhance the pulmonary accumulation of the drug, thereby improving its availability at the target site of action. In this study, we developed a liposomal formulation of I3C and evaluated its lung delivery and chemopreventive potential in tobacco smoke carcinogen [4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK)]-treated mice. Intranasal administration of I3C liposomes led to a ∼100-fold higher lung exposure of I3C than the oral route of administration. Further, intranasal delivery of liposomal I3C led to a significant reduction (37%; p<0.05) in the levels of the DNA adduct formation induced by NNK treatment. Liposomal I3C also significantly increased (by 10-fold) the expression of CYP1A1, a cytochrome P450 enzyme known to increase the detoxification of chemical carcinogens by enhancing their metabolism. Overall, our findings demonstrate that intranasal administration of liposomal I3C has the potential to significantly improve the efficacy of I3C for lung cancer chemoprevention.

Keywords: 4-(Methylnitro-samino)-1-(3-pyridyl)-1-butanone; 4-(Methylnitro-samino)-1-(3-pyridyl)-1-butanone (PubChem CID: 47,289); Cytochrome P450 1A1; DNA adduct; Diindolylmethane (PubChem CID: 3071); Indole-3-carbinol; Indole-3-carbinol (PubChem CID: 3712); Liposomes; O(6)-Methylguanine DNA adduct.