Lipid-based nanodelivery approaches for dopamine-replacement therapies in Parkinson's disease: From preclinical to translational studies

The incidence of Parkinson's disease (PD), the second most common neurodegenerative disorder, has increased exponentially as the global population continues to age. Although the etiological factors contributing to PD remain uncertain, its average incidence rate is reported to be 1% of the global population older than 60 years. PD is primarily characterized by the progressive loss of dopaminergic (DAergic) neurons and/or associated neuronal networks and the subsequent depletion of dopamine (DA) levels in the brain. Thus, DA or levodopa (L-dopa), a precursor of DA, represent cardinal targets for both idiopathic and symptomatic PD therapeutics. While several therapeutic strategies have been investigated over the past decade for their abilities to curb the progression of PD, an effective cure for PD is currently unavailable. Even DA replacement therapy, an effective PD therapeutic strategy that provides an exogenous supply of DA or L-dopa, has been hindered by severe challenges, such as a poor capacity to bypass the blood–brain barrier and inadequate bioavailability. Nevertheless, with recent advances in nanotechnology, several drug delivery systems have been developed to bypass the barriers associated with central nervous system therapeutics. In here, we sought to describe the adapted lipid-based nanodrug delivery systems used in the field of PD therapeutics and their recent advances, with a particular focus placed on DA replacement therapies. This work initially explores the background of PD; offers descriptions of the most recent molecular targets; currently available clinical medications/limitations; an overview of several lipid-based PD nanotherapeutics, functionalized nanoparticles, and technical aspects in brain delivery; and, finally, presents future perspectives to enhance the use of nanotherapeutics in PD treatment.