Intranasal Mucoadhesive Microemulsion of Tacrine to Improve Brain Targeting

Abstract

The aim of the investigation was to prepare and characterize microemulsion/mucoadhesive microemulsion of tacrine (TME/TMME), assess its pharmacokinetic and pharmacodynamic performances for brain targeting and for improvement in memory in scopolamine-induced amnesic mice. The TME was prepared by the titration method and characterized. Biodistribution of tacrine solution and formulations after intravenous and intranasal administrations were evaluated using 99m Tc as marker. From the data, the pharmacokinetic parameters, drug targeting efficiency, and direct nose-to-brain drug transport were calculated. To confirm drug localization in brain gamma scintigraphy in rabbits was performed. Lower Tmax values (60 min) after intranasal compared with intravenous administration (120 min) suggested selective nose-to-brain transport. The brain bioavailability of tacrine after intranasal TMME compared with intranasal tacrine solution was found to be 2-fold higher indicating larger extent of distribution of the drug to brain with intranasal TMME. Rabbit brain scintigraphy also showed higher uptake of drug into the brain after intranasal administration. The results demonstrated rapid and larger extent of transport of tacrine into the mice brain and fastest regain of memory loss in scopolamine-induced amnesic mice after intranasal TMME. Hence, results are suggestive of possible role of intranasal tacrine delivery in treating Alzheimer's patients.

Nanomaterials in controlled drug release

“…Inhalation was generally used to treat diseases relevant to respiratory systems, while the olfactory nerve could also mediate the direct drug delivery from the nasal epithelium into the brain, without crossing the blood-brain barrier (Al-Ghananeem et al 2010;Ali et al 2010;Jogani et al 2008;Kumar et al 2009;Mistry et al 2009a;Nochi et al 2010;Patel et al 2009). The idea originated from the observation that some viral infections can propagate into the brain through the olfactory nerve, and some metal dusts were found in the olfactory bulb of mine workers (Charlton et al 2007;Oberdörster et al 2004).…”

Preparation and in vitro/ex vivo evaluation of nanoemulsion for transnasal delivery of paliperidone

“…Three sheep nasal mucosa pieces (P1, P2, P3) with uniform thickness were selected and mounted on Franz diffusion cells. P1 was treated with 0.5 mL of PBS (pH 6.4, negative control), P2 with 0.5 mL of isopropyl alcohol (positive control), and P3 was treated with PMNE6 for 1 h. After 1 h, the mucosa were rinsed with PBS (pH 6.4) and subjected to histological studies and photographed by microscope (Polarizing Microscope RPL-55 Series, Radical Instruments, India) (Jogani et al 2008;Kumar et al 2008;Patel et al 2009Patel et al , 2013a. Each formulation contains paliperidone 5 mg/mL a PNE4, PNE5 and PNE 6 formulations additionally contain 0.5 %wt/wt of polycarbophil as mucoadhesive agent, and further referred as PMNE4, PMNE5 and PMNE6 respectively Appl Nanosci (2016) 6:1095-1104 1097…”

“…Water was added dropwise to each oilEmix mixture under vigorous stirring. After equilibrium, the samples were visually checked and determined as being clear/transparent (Elshafeey et al 2009;Jogani et al 2008;Kumar et al 2008;Patel et al 2009Patel et al , 2013a.…”

“…Different evaluation parameters such as % drug diffused, flux, diffusion co-efficient and enhancement ratio (E r = -PALI flux at steady state (Jss) of NE formulation/Jss of control vehicle) were derived. The permeation kinetic of PALI from each formulation was evaluated by fitting different kinetic models (Jogani et al 2008;Kumar et al 2008;Patel et al 2009Patel et al , 2013a.…”

“…The globule size was calculated using Stokes-Einstein relationship by Zetasizer Software. Electrophoretic mobility (lm/s) was measured using small volume disposable zeta cell and converted to zeta potential by in-built software using Helmholtz-Smoluchowski equation (Elshafeey et al 2009;Jogani et al 2008;Kumar et al 2008;Patel et al 2009Patel et al , 2013a.…”