Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Lactoferrin-modified organic-inorganic hybrid mesoporous silica for co-delivery of levodopa and curcumin in the synergistic treatment of Parkinson's disease.
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Guo Xiuping, Qiao Xubai, Li Xinru, Zhou Wenkai, Liu Chang, Yu Feifei, Chen Qingbo, Pan Mingyu, Niu Xia, Wang Xiaomei, Li Guiling, Wang Lulu
Аннотация
BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder primarily characterized by oxidative stress and dopaminergic neuron damage. While levodopa remains the cornerstone of PD treatment, its efficacy is limited by poor bioavailability and neuroprotective effects. Curcumin, a potent antioxidant derived from turmeric, demonstrates neuroprotective promise but also suffers from low bioavailability, hindering its therapeutic application. The combined therapeutic use of levodopa and curcumin offers a potential synergistic approach, though its neuroprotection potential through brain-targeted delivery remains underexplored.
PURPOSE: To develop a lactoferrin-modified organic-inorganic hybrid mesoporous silica nanoparticle system (Lf-lip@LC-MSNs) for co-delivering levodopa and curcumin, aiming to enhance neuroprotective efficacy and achieve brain-targeted delivery in PD.
METHODS: Lf-lip@LC-MSNs were engineered to encapsulate levodopa within a curcumin-loaded lipid bilayer, modified with lactoferrin for optimized brain-targeted delivery. In vitro studies were conducted on rotenone-damaged neuronal models to evaluate oxidative stress, mitochondrial dysfunction, α-synuclein aggregation, and neuronal survival. In vivo experiments on MPTP-induced PD mouse models evaluated biodistribution, therapeutic efficacy, and safety in healthy mice, focusing on motor function recovery.
RESULTS: The combination of levodopa and curcumin significantly reduced oxidative stress and α-synuclein accumulation, enhancing neuronal survival compared to monotherapies. Lf-lip@LC-MSNs further amplified these effects, achieving superior brain-targeted delivery and improved motor function restoration with minimal systemic toxicity.
CONCLUSIONS: The combination of curcumin and levodopa provided synergistic neuroprotection in PD models. By employing a targeted delivery system, the Lf-lip@LC-MSNs not only facilitated efficient brain targeting but also potentiated therapeutic outcomes, providing a compelling strategy for treating PD and paving the way for advancements in managing other neurodegenerative diseases.
PURPOSE: To develop a lactoferrin-modified organic-inorganic hybrid mesoporous silica nanoparticle system (Lf-lip@LC-MSNs) for co-delivering levodopa and curcumin, aiming to enhance neuroprotective efficacy and achieve brain-targeted delivery in PD.
METHODS: Lf-lip@LC-MSNs were engineered to encapsulate levodopa within a curcumin-loaded lipid bilayer, modified with lactoferrin for optimized brain-targeted delivery. In vitro studies were conducted on rotenone-damaged neuronal models to evaluate oxidative stress, mitochondrial dysfunction, α-synuclein aggregation, and neuronal survival. In vivo experiments on MPTP-induced PD mouse models evaluated biodistribution, therapeutic efficacy, and safety in healthy mice, focusing on motor function recovery.
RESULTS: The combination of levodopa and curcumin significantly reduced oxidative stress and α-synuclein accumulation, enhancing neuronal survival compared to monotherapies. Lf-lip@LC-MSNs further amplified these effects, achieving superior brain-targeted delivery and improved motor function restoration with minimal systemic toxicity.
CONCLUSIONS: The combination of curcumin and levodopa provided synergistic neuroprotection in PD models. By employing a targeted delivery system, the Lf-lip@LC-MSNs not only facilitated efficient brain targeting but also potentiated therapeutic outcomes, providing a compelling strategy for treating PD and paving the way for advancements in managing other neurodegenerative diseases.