Nanopinion guest column of EUON-ECHA by Prof. Daniel Ruiz-Molina about novel treatment for Parkinson’s disease

Nanopinion guest column of EUON-ECHA by Prof. Daniel Ruiz-Molina about novel treatment for Parkinson’s disease

30 Aug 2021

Prof. Daniel Ruiz-Molina has published a Nanopinion guest column under the framework of the European Union Observatory for Nanomaterials (EUON) and the European Chemicals Agency (ECHA).

Read it (by EUON-ECHA):

Nanotechnology for Parkinson’s treatment: A novel encapsulation approach allows efficient dopamine delivery to the brain

Parkinson’s disease is a common neurodegenerative disorder, which affects more than 10 million people worldwide causing motor impairment and, sometimes, cognitive problems. It is due to the death of so-called dopaminergic neurons in a part of the brain (known as substantia nigra pars compacta), which leads to a deficit of dopamine (DA), one of the main neurotransmitters active in the central nervous system. As a consequence, symptomatic treatment focuses on increasing the concentration of dopamine into the brain.

However, dopamine is not directly administered, because it is unable to cross the blood-brain barrier, a membrane that prevents some of the substances circulating in the blood to penetrate into the nervous system. In order to avoid this limitation, the DA precursor levodopa (L-DOPA) – an amino-acid which participates in the synthesis of dopamine– is given to patients, due to its better ability to cross such barrier. Nevertheless, long-term and intermittent administration of this drug is associated with important disabling complications, such as motor disorders and involuntary muscle movements.

Alternative strategies to guarantee a continuous supply of dopamine to the brain, without incurring in such complications, is much needed. Nano-encapsulation is being increasingly explored for drug delivery, since smartly-designed nanocarriers can travel throughout the body avoiding the effect of metabolisms and release substances when the desired target is reached.

Since nanoencapsulation and synthesis of structures for drug delivery are among my interests and the topics of expertise of the Nanostructured Functional Materials Group, which I lead at the Catalan Institute of Nanoscience and Nanotechnology (ICN2) in Barcelona, I decided to take on this challenge, together with other researchers and students in my group. We developed this study, recently published in ACS Nano, in collaboration with scientists from the Protein Engineering Group, led by Dr Julia Lorenzo, at the Institute of Biotehcnology and Biomedicine (IBB) of the Universitat Autònoma de Barcelona (UAB), and from the Neurodegenerative Diseases group of Vall d’Hebron Research Institute (VHIR) in Barcelona, led by Prof. Miquel Vila.

The main objective of our work was to obtain a “nanoplatform” – in other words, a biocompatible nano-structure embedding the substance to be delivered – able to reach the brain through a noninvasive route and to generate a slow and controlled release of dopamine. We took inspiration from nature, specifically from neuromelanin, to develop a tailor-made nanoscale coordination polymer (NCP) characterized by the reversible incorporation of DA as its principal component. In fact, neuromelanin particles are found in dopaminergic neurons and are mainly made of dopamine, but they cannot release such dopamine, since it is covalently and irreversibly bonded. For this reason, we have designed a related bioinspired nanoparticle, where the dopamine is linked via reversible coordination bonds. These connections are broken, and the dopamine liberated, at different pHs or in the presence of body proteins, among others.

Once we developed the optimal synthesis procedure for these nanoparticles, named dopamine nanoscale coordination polymers (DA-NCPs), we tested them both in vitro and in vivo in rats. Intranasal (via the nose) administration showed a relevant biocompatibility and non-toxicity of DA-NCPs, as well as a fast and efficient distribution of dopamine in the central nervous system of the animals (avoiding the blood-brain barrier). Our nanoparticles proved to be effective in delivering dopamine to the brain and, thus, in reversing Parkinson’s symptoms. In addition, the synthetic methodology that we used is simple, cheap, and exhibited a very satisfactory yield. Indeed, the dopamine-loading efficiency reached values of up to 60%, which are among the highest reported to date. This favors the treatment effectiveness and reduces the systemic side effects, since the medicament can be administered in more controlled and sustained doses.

We believe that 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 to the development of other platforms able to deliver a wide range of drugs into the brain in a controlled manner, for the treatment of other diseases, such as brain tumours, Alzheimer’s and Epilepsy. Overall, these experiments certainly demonstrate the value of nanotechnology in the treatment of brain disorders.

See the full Nanopinion!

Our published paper in ACS Nano

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