Levodopa(L-DOPA),a precursor of dopamine,is commonly prescribed for the treatment of the Parkinson’s disease(PD).However,oral administration of levodopa results in a high level of homocysteine in the peripheral circu...Levodopa(L-DOPA),a precursor of dopamine,is commonly prescribed for the treatment of the Parkinson’s disease(PD).However,oral administration of levodopa results in a high level of homocysteine in the peripheral circulation,thereby elevating the risk of cardiovascular disease,and limiting its clinical application.Here,we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature.The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid(TA)/polyvinyl alcohol(PVA)via hydrogen bonding using the flash nanocomplexation(FNC)process,resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner.Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase,which indicate the dopaminergic neuron functions,were increased by 2-and 4-fold,respectively.Movement disorders and cerebral oxidative stress of the rats were significantly improved.This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs.This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.展开更多
基金supported by Natural Science Foundation of China(No.51533009)the Guangdong Innovative and Entrepreneurial Research Team Program(No.2013S086)the key Area Research and Development of Guangzhou(No.202007020006).
文摘Levodopa(L-DOPA),a precursor of dopamine,is commonly prescribed for the treatment of the Parkinson’s disease(PD).However,oral administration of levodopa results in a high level of homocysteine in the peripheral circulation,thereby elevating the risk of cardiovascular disease,and limiting its clinical application.Here,we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature.The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid(TA)/polyvinyl alcohol(PVA)via hydrogen bonding using the flash nanocomplexation(FNC)process,resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner.Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase,which indicate the dopaminergic neuron functions,were increased by 2-and 4-fold,respectively.Movement disorders and cerebral oxidative stress of the rats were significantly improved.This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs.This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.
