Intranasal delivery of liposomal indole-3-carbinol improves its pulmonary bioavailability.
Intranasal delivery of liposomal indole-3-carbinol improves its pulmonary bioavailability.
复制标题
脂质体吲哚-3-甲醇的鼻内递送提高了其肺生物利用度。
DOI：
10.1016/j.ijpharm.2014.10.018
复制
发表时间：
2014
影响因子：
5.8
通讯作者：
Kassie,Fekadu
中科院分区：
文献类型：
--
作者：
Song,JungMin;Kirtane,AmeyaR;Upadhyaya,Pramod;Qian,Xuemin;Balbo,Silvia;Teferi,Fitsum;Panyam,Jayanth;Kassie,Fekadu
Indole-3-carbinol (I3C), a constituent of commonly consumedBrassicavegetables, 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.
