Nose-to-Brain delivery of genistein-loaded peppermint lipid nanocapsules for neuroprotection against Alzheimer's Disease: Formulation, Characterization, pharmacokinetic and Pharmacodynamic studies.

Lipid nanocapsules (LNC) are promising nanocarriers that have known mucus permeation enhancement properties, this makes them suitable for intranasal administration. They could act as potential nose-to-brain carriers for drugs like genistein with poor aqueous solubility and extensive metabolism, making them reach the brain in effective concentrations. This study was conducted to observe the effects of different essential oils (peppermint, lavender, and eucalyptus essential oils) on LNC characteristics including particle size, polydispersity index, and zeta potential. The optimized genistein-loaded peppermint LNC experienced a nearly full in-vitro release in 10 h. Transmission electron microscope, differential scanning calorimetry, and Fourier-transform infrared spectroscopy ensured the successful preparation of this formulation. In-vivo pharmacokinetic study revealed that the optimized LNC had better relative bioavailability than drug suspension by 60% with earlier T max at 30 min and C max of 23.17 ± 1.5 µg/g brain tissue. Pharmacodynamic assessment in AlCl3-induced Alzheimer's disease in rats showed that the optimized LNC preserved the spatial and reference memory in Morris water maze test. Biochemical analyses confirmed the enhanced oxidative defense (increased superoxide dismutase, reduced glutathione, and decreased malondialdehyde) and the inhibition of acetylcholinesterase enzyme. Histopathological examination showed preserved neuronal structure in the hippocampal brain region. Genistein-loaded peppermint LNC were able to have neuroprotective effects, making the intranasal LNC formulation a promising candidate for the neuroprotection against Alzheimer's disease.