Hisham A. Nematalla, Mona Elharoun, Mohammad M. Abd‐Alhaseeb, Hend A. Sharafeldin, Manal A Elsheikh, Haidy Abbas, Amr Elkelish, Komla Mawunyo Dossouvi, Amir E. Mehana, Fathy Elsayed Abdelgawad, Mariam Zewail
BACKGROUND: Tremors and rigid muscles are symptoms of Parkinson's disease (PD), which affects about 1% of the global population. PURPOSE: To investigate the integrated therapeutic benefits of the phytopharmaceutical berberine and mucoadhesive nanoliposomes, administered via the nose-to-brain route, to enhance bioavailability, facilitate blood-brain barrier penetration, and augment efficacy against neurodegenerative progression in Parkinson's disease (PD). STUDY DESIGN: This study aimed to develop and characterize chitosan-decorated liposomes (chitosomes) loaded with berberine (BER) for targeted brain delivery via the intranasal route. METHODS: In vitro characterization of BER loaded chitosomes was conducted including measurement of particle size, zeta potential, EE % and in vitro drug release. The optimized formulation was intranasally administered in rats with rotenone-induced PD animal model, motor function and coordination were investigated besides testing the levels of different biomarkers and histopathological examination. RESULTS: The prepared chitosomes had a particle size of 312 nm, zeta potential of 34 mV, and high encapsulation efficiency (89.3%) and sustained drug release. In vivo assessments conducted in a rotenone-induced PD animal model revealed notable improvements in motor function and coordination. Biochemical evaluations showed that BER chitosomes reduced α-synuclein by 49% and raised dopamine levels by 55% as compared to the model group. Additionally, BER chitosomes significantly decreased oxidative stress markers by a 67% decrease in NF-κB levels and a one-fold increase in Nrf2. Histological examination showed a noticeable reduction in neuronal degeneration and Lewy body formation. CONCLUSION: Our findings imply that BER chitosomes are a viable intranasal delivery tool for the efficient treatment of PD due to their enhanced bioavailability. and greater nasal mucosa penetration.