1Division of Cyclotron and Radiopharmaceutical Sciences, Brig. SK Mazumdar Road, Delhi-110054
2Department of Pharmaceutics, MS University Baroda
The aim of this study investigation was to prepare microemulsions containing tacrine HCl (T) for rapid drug delivery to brain to treat mild to moderate forms of Alzheimer's disease and to evaluate biodistribution in mice. Tacrine micro emulsions (TME) were prepared using titration method and were characterized by globule size distribution and zeta potential.
TME was radiolabeled using technetium-99m (99mTc) and radiolabeled-drug formulations of (T) were used to carry out biodistribution of drug in brain of mice after intravenous and intranasal administration. The direct nose to brain transport (%DTP), drug targeting efficiency (%DTE) and pharmacokinetics parameters were calculated.99mTc labeled drug formulation of Tacrine were found to be stable and suitable to perform in vivo studies. Following intra nasal administration of TMME, TME, TS, and intravenous administration of TS.
Brain/blood uptake ratio at 0.5 hours were found to be highest in intranasal TMME, followed by intranasal TME, intranasal TS, and finally intravenous TME indicating effective brain targeting following intranasal administration of TTME. Comparing intranasal administration of TTME with intravenous administration of TME, the % DTE,%DTP were found higher indicating better drug transport following intranasal administration and highest brain-targeting following TTME administration as it passes through olfactory pathways reaching brain bypassing BBB.
Brain scintigrams show substantial uptake of Tacrine into brain after intranasal administration of TTME.
The study demonstrated faster and larger rate of transport into the brain following intranasal administration of TTME and it has substantial potential in better management of CNS disorders like Alzheimer's disease.
