Liquid crystal precursor for nose to brain targeting delivery of donepezil: plasma and brain pharmacokinetics

Donepezil is used in the Alzheimer’s disease by the oral route, but several side effects have been reported. Considering the advantages of the intranasal route, a mucoadhesive lyotropic liquid crystal precursor (LLCP) was developed and characterized for nose to brain delivery of donepezil, combining CETETH-10, oleic acid, and water. For an in vivo assessment, LLCP was administered to Wistar rats by intranasal route and the plasma and brain pharmacokinetics were compared to oral and intranasal solution (Protocol Ethics Committee nº 28/2018 CEUA-UNIFAL/MG). The intranasal administration resulted in a faster brain targeting exhibiting lower tmax than the oral administration. However, the intranasal administration of the LLCP presented higher values of Cmax, AUC, and t1/2 than the nasal solution. Then, the intranasal administration of the donepezil using LLCP may be a promising strategy for the treatment of Alzheimer’s disease, reducing side effects, promoting brain targeting and prolonging drug half-life.