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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.
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Details
1 Universidade de Brasília, Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Brasília, Brazil (GRID:grid.7632.0) (ISNI:0000 0001 2238 5157)
2 Universidade de Brasília, Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Brasília, Brazil (GRID:grid.7632.0) (ISNI:0000 0001 2238 5157); Universidade Estadual de Londrina, Departamento de Biologia Animal e Plantas, Centro de Ciências Biológicas, Londrina, Brazil (GRID:grid.411400.0) (ISNI:0000 0001 2193 3537)
3 Universidade de Brasília, Laboratório de Neurofarmacologia, Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Brasília, Brazil (GRID:grid.7632.0) (ISNI:0000 0001 2238 5157); Universidade Federal de Catalão, Laboratório de Fisiologia e Farmacologia, Goiás, Brazil (GRID:grid.7632.0)
4 Universidade de São Paulo, Departamento de Química, Centro de Nanotecnologia e Engenharia de Tecidos-Fotobiologia e Fotomedicina, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Ribeirão Preto, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722)
5 Universidade Católica de of Brasília, Brasília, Brazil (GRID:grid.411952.a) (ISNI:0000 0001 1882 0945)
6 Universidade Federal de Goiás, Instituto de Saúde Pública e Patologia Tropical, Goiânia, Brazil (GRID:grid.411195.9) (ISNI:0000 0001 2192 5801)
7 Universidade de Brasília, Laboratório de Imunologia Aplicada, Departamento de Biologia Celular, Instituto de Ciências Fisiológicas, Brasília, Brazil (GRID:grid.7632.0) (ISNI:0000 0001 2238 5157)