• In a study recently published in the American Chemical Society’s Journal ACS Nano, polymeric nanoparticles inspired by natural neuromelanin were used to encapsulate dopamine and for intranasal administration to reach the brain for treatment of Parkinson’s disease. The effectiveness of this technique was tested in rats.
• The work was coordinated by Dr Daniel Ruiz-Molina, Leader of the Nanostructured Functional Materials Group at the BIST centre ICN2 (Catalan Institute of Nanoscience and Nanotechnology), and Dr Julia Lorenzo, Leader of the Protein Engineering Group at the Institute of Biotechnology and Biomedicine (IBB) at the Unviersitat Autònoma de Barcelona (UAB).
• The research was developed in collaboration with the Neurodegenerative Diseases group at the Vall d’Hebron Research Institute (VHIR), led by Prof. Miquel Vila.
Barcelona, Tuesday June 1, 2021. Parkinson’s disease (PD) is a common neurodegenerative disorder caused by the death of dopaminergic neurons in part of the brain (known as substantia nigra pars compacta), which leads to a deficit in dopamine (DA), one of the main neurotransmitters active in the central nervous system. Symptomatic treatment focuses on increasing the concentration of dopamine in the brain.
However, dopamine cannot be administered directly because it cannot cross the so-called blood-brain barrier, which prevents some of the substances circulating in the blood from penetrating the nervous system. Thus, the DA precursor levodopa (L-DOPA) –an amino-acid involved in the synthesis of dopamine– is used due to its better ability to cross this barrier. Nevertheless, long-term and intermittent administration of this drug is associated with disabling complications, including motor disorders and involuntary muscle movements.
In a paper recently published in ACS Nano, the use of synthetic melanin-like nanoparticles to overcome these limitations is described. The research was coordinated by Dr Daniel Ruiz-Molina, leader of the ICN2 Nanostructured Functional Materials Group, and Dr Julia Lorenzo, leader of the Protein Engineering Group at the Institute of Biotehcnology and Biomedicine (IBB) of the Universitat Autònoma de Barcelona (UAB), and was developed in collaboration with the Neurodegenerative Diseases group of Vall d’Hebron Research Institute (VHIR), led by Prof. Miquel Vila.
The main objective of the work was to obtain a “nanoplatform”, which is a biocompatible nano-structure with the substance to be delivered, able to reach the brain through a noninvasive route and generate a slow and controlled release of dopamine. A tailor-made nanoscale coordination polymer (NCP), characterised by the reversible incorporation of DA as its principal component, was tested in vitro and in vivo in rats. Intranasal administration of these nanoparticles, called DA-NCPs, showed a relevant biocompatibility, non-toxicity, and a fast and efficient distribution of dopamine in the central nervous system of the animals (avoiding the blood-brain barrier).
As reported by the researchers, the proposed method is effective in delivering dopamine to the brain and thus in reversing Parkinson’s symptoms. In addition, the synthetic methodology used is simple, cheap, and exhibited a satisfactory yield (with a DA loading efficiency of up to 60%).
These findings establish nanoscale coordination polymers as promising future candidates for efficient nasal delivery of drugs to the central nervous system, and thus for the symptomatic treatment of people affected by Parkinson’s and other neurodegenerative disorders. This type of nano-formulation and administration route may also pave the way for the development of other platforms able to deliver a wide range of drugs into the brain in a controlled manner, for the treatment of various brain diseases (such as brain tumours, Alzheimer’s, and Epilepsy).