Enhanced cognitive function in mice through intranasal delivery of sinapic acid via chitosan-coated solid lipid nanoparticles

Abstract

Sinapic acid (SAc) is a plant-based antioxidant known for its neuroprotective effects. However, its therapeutic potential for Alzheimer's disease (AD) remains limited because of its low bioavailability in the brain. Therefore, the present study hypothesized safe and effective delivery of SAc using chitosan-coated solid lipid nanoparticles (Cs-SAc-SLNs) via the intranasal route for AD treatment. The characterization of Cs-SAc-SLNs using AFM, SEM, and TEM confirmed their spherical morphology with a particle size of less than 200 nm. Moreover, the Cs-SAc-SLNs demonstrated a sustained drug release of 61.3 ± 1.7 % in 24 h. Remarkably, Cs-SAc-SLNs showed significant cellular uptake (P < 0.05) than uncoated SLNs in the Neuro-2a cell line. The histopathology study using nasal mucosa demonstrated the safety of the formulation, which makes it ideal for intranasal administration. The in vitro sustained drug release is well mapped with the in vivo pharmacokinetics study, indicating a 1.7-fold increase in the half-life (t_1/2) of SAc. Interestingly, the chitosan-coated Cs-SAc-SLNs (i.n.) demonstrated a superior AUC_0-∞ (3128.05 ± 129.42 ng/g*h) and showed a significant enhancement in brain bioavailability (3.7-fold) in terms of drug targeting efficiency as compared to plain SAc (i.v.). This improved brain delivery contributed to substantial neuroprotective effects in Aβ_1-42-induced cognitively impaired mice. The study also supported the decreased biochemical markers levels of oxidative stress, cholinergic activity, and inflammatory cytokine levels (TNF-α) in the hippocampus and cortex of Aβ_1-42-injected mice. Overall, the present study highlights the safe and enhanced cognitive function using chitosan-coated SLNs for AD treatment.

Keywords: Alzheimer’s disease; Chitosan; Herbal drug; Lipid nanoparticles; Sinapic acid; Solid lipid nanoparticles.