Dopamine-loaded nanoparticle systems circumvent the blood–brain barrier restoring motor function in mouse model for Parkinson’s Disease
Victoria Monge‐Fuentes, Andréia Biolchi Mayer, Marcos Robalinho Lima, Luiza Ribeiro Geraldes, Larissa Nepomuceno Zanotto, Karla Graziella Moreira, Olímpia Paschoal Martins, Henrique Luís Piva, Maria Sueli Soares Felipe, André Corrêa Amaral, Anamélia Lorenzetti Bocca, Antônio Cláudio Tedesco, Márcia Renata Mortari
Abstract
Parkinson's disease (PD) is a progressive and chronic neurodegenerative disease of the central nervous system. Early treatment for PD is efficient; however, long-term systemic medication commonly leads to deleterious side-effects. Strategies that enable more selective drug delivery to the brain using smaller dosages, while crossing the complex brain-blood barrier (BBB), are highly desirable to ensure treatment efficacy and decrease/avoid unwanted outcomes. Our goal was to design and test the neurotherapeutic potential of a forefront nanoparticle-based technology composed of albumin/PLGA nanosystems loaded with dopamine (ALNP-DA) in 6-OHDA PD mice model. ALNP-DA effectively crossed the BBB, replenishing dopamine at the nigrostriatal pathway, resulting in significant motor symptom improvement when compared to Lesioned and L-DOPA groups. Notably, ALNP-DA (20 mg/animal dose) additionally up-regulated and restored motor coordination, balance, and sensorimotor performance to non-lesioned (Sham) animal level. Overall, ALNPs represent an innovative, non-invasive nano-therapeutical strategy for PD, considering its efficacy to circumvent the BBB and ultimately deliver the drug of interest to the brain.