Abstract
Carmustine is used in the treatment of glioblastoma (GBM). GBM is well-known life-threatening type of cancerous tumor. GBM covers 60.00 % among all primary brain tumors, with an occurrence of 74,000 cases across the globe. Management for GBM is still very difficult because most of the medicines are unable to cross the blood-brain barrier (BBB). The present work observed that flexible liposomes embedded in-situ nasal gel of carmustine is the best brain-targeted medicine delivery system for the management of GBM through the nasal route. To evaluate in-vivo pharmacokinetic parameters of carmustine formulations administered through nasal routes in Wistar rats. In this work, different pharmacokinetic parameters were determined for carmustine formulations viz. carmustine API (Active Pharmaceutical Ingredient) solution, flexible liposomes, in-situ thermoreversible intranasal gel, optimized flexible liposomes embedded in-situ thermoreversible intranasal gel via intranasal administration in rats, and compared with marketed intravenous injection of carmustine administered through intravenous route. Carmustine was estimated with the help of a validated high-performance liquid chromatography (HPLC) approach. Three to four-months-old normal Wistar rats of either sex, having a weight of 200-250 grams were used in this study. Intranasal administration of optimized flexible liposomes embedded in-situ nasal gel showed greater Cmax (∼two-fold), AUC0→t (∼three-fold), AUC0→∞ (∼six-fold), & decreased Tmax (1 h) data in the brain, than commercial intravenous injection of carmustine. The plasma concentration of carmustine administered through nasal route was found to be comparatively lower than intravenous administration, indicating lower systemic exposure to carmustine via the nasal route. In-vivo pharmacokinetics results revealed that the optimized flexible liposomes embedded in-situ nasal gel of carmustine can effectively deliver carmustine to brain by nasal drug delivery system in Wistar rats.
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