Intranasal administration of in silico designed Rivastigmine mucoadhesive nanoparticles ameliorates scopolamine-induced Alzheimer's symptoms in mice: Pharmacokinetic and pharmacodynamic evidences.

The low oral bioavailability (36 %) of rivastigmine tartrate (RT), and the inconspicuous pharmacological target site has necessitated the need to explore alternative routes of delivery for effective management of Alzheimer's disease (AD). The current study aimed to develop in silico designed polymeric nanoparticles (NPs) for the intranasal delivery of RT. Eudragit RL 100 (EDRL) was selected as mucoadhesive polymer because of its optimum binding affinity with RT and nasal mucin. These NPs were prepared using spray drying method by utilizing QbD approach. Yield, particle size, zeta potential, entrapment efficiency and drug loading were optimized using central composite design. Furthermore, the TEM and SEM analysis of RT-EDRL NPs, respectively, revealed the particle size in the range of 50-100 nm and their spherical shape. The in vitro and ex vivo release profiles revealed sustained drug release from RT-EDRL NPs as compared to RT solution. The intranasal administration of optimized NPs exhibited higher RT concentration in mice brain as compared to other routes. Higher direct transport percentage (DTP %) and drug targeting efficiency (DTE %) indicated direct transport of RT to the brain through the nose and was better than that observed after application of transdermal patch. The neuroprotective potential conferred by intranasal administration of in silico designed NPs in scopolamine induced amnesia mice seems to be a potential brain targeted delivery system for effective management of AD.