Brain Targeted Drug Delivery System of Carmustine: Design, Development, Characterization, in vitro, ex vivo Evaluation and in vivo Pharmacokinetic Study

Abstract

The treatment of gliomas remains difficult task. Carmustine is a drug that is used in the treatment of gliomas. Flexible liposomes embedded in situ thermoreversible nasal gel preparations of Carmustine were studied for in vitro carmustine release, ex vivo carmustine permeation and carmustine release kinetics. The epithelial layers of nasal tissue were found to be intact and undamaged during histological analysis. Intranasal administration of optimized flexible liposomes embedded in a nasal gel showed higher Cmax (Approximately two-fold), AUC0→t (Approximately three-fold), AUC0→∞ (Approximately six-fold), and lower Tmax (1 h) in the brain, compared to intravenous injection of carmustine. The present study demonstrates that the flexible liposome embedded thermoreversible in situ intranasal gel of carmustine improved the targeted uptake of carmustine in the brain through the nasal delivery system and could be a reliable and effective delivery system for carmustine in the treatment of gliomas.