Objective: To evaluate the pharmacokinetic profile and neuroprotective efficacy of intranasally administered berberine-loaded solid lipid nanoparticles (BE-SLN) in a streptozotocin (STZ)-induced rat model of Alzheimer’s disease (AD).

Background: The clinical translation of many promising neuroprotective compounds, including the multimodal alkaloid berberine, is severely restricted by poor blood-brain barrier (BBB) permeability. Nanocarrier-mediated intranasal delivery presents a promising, non-invasive strategy to bypass the BBB via the olfactory and trigeminal neural pathways, facilitating direct central nervous system (CNS) access.

Method: BE-SLNs were synthesized utilizing a double-emulsion solvent displacement method and optimized for mucosal uptake. An AD-like phenotype was established in Wistar rats via intracerebroventricular STZ infusion. Comparative CNS pharmacokinetics were analyzed between intranasal and intravenous administration routes. Cognitive outcomes were quantified using radial arm, elevated plus, and passive avoidance mazes. Biochemical evaluations measured amyloid-β42 (Aβ42), total tau, acetylcholinesterase, monoamine oxidase, malondialdehyde, and pro-inflammatory cytokine profiles

Results: Intracerebroventricular STZ successfully induced profound cognitive deficits, Aβ42/tau accumulation, and neuroinflammation. The engineered BE-SLNs exhibited an optimal mean particle diameter of 58.4 nm. Crucially, intranasal instillation achieved markedly superior and prolonged CNS berberine concentrations compared to intravenous systemic delivery. BE-SLN intervention significantly restored cholinergic tone and antioxidant capacity, while drastically attenuating Aβ42 aggregation, total tau expression, and lipid peroxidation (p < 0.001). These biochemical reversals correlated with significant improvements in spatial memory and behavioral performance across all maze paradigms.

Conclusion: Nanoparticle-facilitated intranasal delivery of berberine effectively bypasses the BBB, delivering potent, targeted neuroprotection in a preclinical AD model. This non-invasive approach significantly reverses molecular pathology and cognitive decline, highlighting the transformative potential of lipid nanocarriers in advancing neuropharmacological treatments for Alzheimer’s disease and related dementias.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intranasal-delivery-of-berberine-loaded-solid-lipid-nanoparticles-ameliorates-neuropathological-and-behavioral-deficits-in-a-preclinical-alzheimers-model/