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Intranasal Delivery of Berberine via QbD-Engineered Chitosan Coated Liposomes: Formulation Fabrication and Cellular Efficacy for Alzheimer’s Intervention
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DOI：10.1007/s12668-026-02777-1.png)
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Abstract
En 中文
Berberine (BER) is a natural alkaloid with intrinsic anti-inflammatory, antioxidant properties, and a neuroprotective role in Parkinson’s disease, cerebral ischemia, epilepsy, and Alzheimer’s disease. Nonetheless, its clinical efficacy is hindered by its low oral bioavailability and poor ability to traverse the BBB. The primary schedule of the proposed research is to evaluate the neuroprotective role of BER in Alzheimer’s disease (AD). In the current investigation, we developed intranasal chitosan-coated BER-laden liposomes (CH-BER Lipo) for AD management. In this study, BER Lipo was optimized using a Box-Behnken design and coated with chitosan (CH) to enhance mucoadhesion and nasal residence, and to reduce mucociliary clearance. The chitosan anchoring enhanced the vesicle size and surface charge of BER Lipo, increasing from 144.9 ± 3.50 nm to 177.73 ± 1.61 nm and from − 19.20 mV to + 34.09 mV, as evident from TEM analysis. During mucin interaction studies, the vesicle size of CH-BER Lipo was enhanced from 177.73 ± 1.61 nm to 195.10 ± 6.55 nm, and surface charge was reduced from + 34.09 mV to + 15.4 mV, validating its mucoadhesive potential. Cell viability studies revealed that CH-BER Lipo exhibits neuroprotective action against scopolamine (SCOP)-induced AD in SH-SY5Y cells. CH-BER Lipo further demonstrated improved cellular internalization (1.44- and 2.46-fold) in neuronal cells, with significant reductions in cell death (2.78- and 3.81-fold) and reactive oxygen species (ROS), while restoring mitochondrial health (1.21- and 1.97-fold) in neuronal cells. In a nutshell, CH-BER Lipo via the intranasal route could be a promising preliminary approach for further investigation in AD management.
Keywords:
Liposomes
Box-Behnken design
Alzheimer’s disease
Mucoadhesion
Chitosan
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