Chitosan-coated nanostructured lipid carriers for intranasal delivery of sinapic acid in Aβ1-42 induced C57BL/6 mice for Alzheimer's disease treatment.

Sinapic acid (SA) is a plant-derived antioxidant that exhibits neuroprotective activity. However, its poor bioavailability in the brain limits its therapeutic application in treating Alzheimer's disease (AD). Therefore, the present study hypothesizes that coating nanostructured lipid carriers (NLCs) with a biological macromolecule like chitosan (CH-SA-NLCs) could enhance the delivery of SA for AD treatment. The CH-SA-NLCs were spherical with sizes below 200 nm, confirmed by AFM, SEM, and TEM and achieved a sustained drug release of 76.5 % in pH 6.5 simulated nasal fluid over 24 h. Moreover, the histopathology study confirmed the safety of CH-SA-NLCs, validating its suitability for intranasal administration. Not only the in vitro sustained drug release closely correlated with in vivo pharmacokinetics of CH-SA-NLCs (i.n.), demonstrating a 1.7-fold increase in SA's half-life compared to plain SA (i.v.) in plasma but also CH-SA-NLCs (i.n.) achieved a superior AUC0-∞ of 7676.32 ± 2738.55 ng/g*h with a 2.6-fold improved drug targeting efficiency of SA in the brain of BALB/c mice. These improvements resulted in significant neuroprotective effects and decreased oxidative stress and inflammatory levels in Aβ1-42-induced mice. Overall, the study highlights safe and effective intranasal delivery of SA via chitosan-coated nanocarrier as a promising AD treatment strategy.