Mitochondria-Targeted Delivery Strategy of Dual-Loaded Liposomes for Alzheimer's Disease Therapy.

Liposomes modified with tetradecyltriphenylphosphonium bromide with dual loading of α-tocopherol and donepezil hydrochloride were successfully designed for intranasal administration. Physicochemical characteristics of cationic liposomes such as the hydrodynamic diameter, zeta potential, and polydispersity index were within the range from 105 to 115 nm, from +10 to +23 mV, and from 0.1 to 0.2, respectively. In vitro release curves of donepezil hydrochloride were analyzed using the Korsmeyer-Peppas, Higuchi, First-Order, and Zero-Order kinetic models. Nanocontainers modified with cationic surfactant statistically better penetrate into the mitochondria of rat motoneurons. Imaging of rat brain slices revealed the penetration of nanocarriers into the brain. Experiments on transgenic mice with an Alzheimer's disease model (APP/PS1) demonstrated that the intranasal administration of liposomes within 21 days resulted in enhanced learning abilities and a reduction in the formation rate of Aβ plaques in the entorhinal cortex and hippocampus of the brain.