PRELIMINARY STUDIES ON BRAIN TARGETING OF INTRANASAL ATOMOXETINE LIPOSOMES

Objective: The objective of the present study was to evaluate the enhancement in brain uptake of liposomes containing atomoxetine (ATX-Lipo) for intranasal delivery in the management of Attention Deficit Hyperactivity Disorder (ADHD).Methods: ATX-Lipo and ATX mucoadhesive liposomes (ATX-Muco Lipo) with and without a vasoconstrictor phenylephrine (PHE) were prepared by lipid film hydration method and characterized for physicochemical parameters. Biodistribution and pharmacokinetic evaluation of ATX-Lipo in the brain and blood of Sprague Dawley rats following intranasal (i. n.) and intravenous (i. v.) administrations were examined using optimized technetium-labeled ([99]m Tc-labeled) atomoxetine formulations. Gamma scintigraphy imaging was performed in Sprague Dawley rats.Results: ATX-Lipo and ATX-Muco Lipo were found to be stable with average particle size of 404.35±1.86 nm and 510.50±1.22 nm respectively.[99]mTc tagged ATX-Lipo, ATX-Muco Lipo, ATX+PHE-Muco Lipo and ATX solution were found to be stable and suitable for in vivo studies. On comparing ATX concentrations after i. n. administrations of ATX-Lipo, ATX-Muco Lipo and ATX+PHE-Muco Lipo and i. v. administration of ATX-Lipo, brain/blood uptake ratios (BBR) at 30 min were found to be 0.161, 1.255, 0.331, and 0.003 respectively. These results revealed effective brain targeting following i. n. administration of mucoadhesive ATX liposomes. Higher drug targeting efficiency (% DTE) and direct transport percentage (%DTP) for mucoadhesive liposomes indicated considerable brain targeting from ATX-Muco liposomes. Gamma scintigraphy imaging of the rat brain conclusively demonstrated the greater extent of transport of atomoxetine by ATX+PHE-Muco Lipo (i. n.), when compared with ATX solution (i. n.) into the rat brain.Conclusion: This preliminary investigation demonstrates a considerable extent of transport of ATX into the brain through i. n. ATX+PHE-Muco Lipo, which may prove to be a new platform for better management of ADHD.Keywords: Intranasal delivery, Brain targeting, Mucoadhesive liposomes, Vasoconstrictor, Radiolabeling, Drug targeting efficiency, Direct transport percentage, Gamma scintigraphy