A novel nanocomposite Lf-DA-MSN-PF127 aided the delivery of dopamine for the treatment of Parkinson's disease in a rat model

Abstract

Dopamine is a pivotal neurotransmitter in the central nervous system, which is instrumental in motor functions. Parkinson's Disease (PD) is a chronic, progressive, age-related neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra in the midbrain, resulting in the reduction of dopamine levels. Levodopa is a prescribed medicine for symptomatic relief of PD, as it is an amino acid precursor of dopamine that readily crosses the Blood–Brain Barrier (BBB). However, levodopa exhibits poor plasma bioavailability and limited brain uptake, and induces peripheral side effects. To overcome this biological impediment, we have developed and characterized a lactoferrin-functionalized Pluronic F-127 capped dopamine-loaded mesoporous silica nanocomposite (Lf-DA-MSN-PF127) to furnish dopamine across the BBB. In vivo experiments using a rotenone (ROT) induced PD rat model confirmed that Lf-DA-MSN-PF127 crosses the BBB and delivers dopamine. It remarkably boosts motor symptoms and dopamine levels in ROT-induced PD rats. Our study illustrates the nontoxic effect of the Lf-DA-MSN-PF127 nanocomposite and its efficacy in delivering dopamine across the BBB, providing a novel treatment strategy for PD.