Dopamine-loaded nanoparticle systems circumvent the blood-brain barrier restoring motor function in mouse model for Parkinson's Disease

Sci Rep. 2021 Jul 26;11(1):15185. doi: 10.1038/s41598-021-94175-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain / drug effects
  • Brain / metabolism
  • Disease Models, Animal
  • Dopamine / administration & dosage*
  • Dopamine / pharmacokinetics*
  • Dopaminergic Neurons / drug effects
  • Drug Delivery Systems*
  • Humans
  • Male
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Nanotechnology
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism*
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Oxidopamine
  • Dopamine