Personalised gold eye drops

by Valérie Levée

Nothing must enter the eye and one of the barriers against intruders is the tear film. However, this tear film also blocks the path followed by the drugs contained in eye drops. Less than 0.02% of active molecules cross the cornea. To reduce such losses, there is a solution: delivering drugs up to the cornea by means of gold particles!

“Our gold particles are ultra-stable, biologically inert, adhesive and their polymer shell enables drug encapsulation,” reels off Élodie Boisselier, assistant professor at the Department of Ophthalmology and Otolaryngology /Head and Neck Surgery of the Faculty of Medicine of Université Laval.

Let us take a deep dive into these particles to get a better insight. At the centre there is a tiny sphere composed of gold atoms and stabilised by a shell of sulfur atoms. “Sulfur is gold’s best friend,” continues Élodie Boisselier. “In order to load drugs, we wrap the metallic core with polyethylene glycol (PEG) molecules, which form a mesh where we can place the drugs,” adds Gabrielle Raîche-Marcoux, the PhD student working on this project.

And what about adhesion? It happens that the innermost layer of the tear film, the one in contact with the cornea, is composed of mucins. These are cysteine-rich proteins, which is especially interesting because cysteine is an amino acid that contains a sulfur atom. When the gold particles approach mucins, the protein sulfur atoms bind to create disulfide bridges.

These bridges are supposed to anchor gold particles to the cornea while the drugs are being released and exert their effect.
This is the theory. In actual fact, one has to work out the optimal synthetic conditions, i.e. fine-tuning the length of PEG molecules, the drug loading, or how long they will remain trapped in the carrier (residence time)… “As a function of the ratios between drugs and particles, I measure how many molecules come in and at which rate; as a function of the residence time, I look at the molecular-level organisation of the drugs in the carrier,” describes Gabrielle Raîche-Marcoux. In order to determine the result of her chemical syntheses, she stares into the transmission electron microscope to get an image of the metallic core. Dynamic light scattering shows her the overall aspect of the particle and UV-Visible spectroscopy enables Gabrielle to discriminate between particles according to their absorption band. “The position of the absorption band is sensitive to the chemical environment surrounding the metallic particle core,” explains Gabrielle Raîche-Marcoux.

“Gabrielle’s main goal is to synthesise particles, to characherise the physico-chemical features and to control the loading and release properties,” summarises Élodie Boisselier.
In parallel, associate professor Stéphanie Proulx’s research group, in the same research unit as Élodie Boisselier, has developed a device equipped with a post-mortem cornea to mimic the eye. This device will enable the study of the distribution of the particles at the corneal surface and the fate of drugs and gold particles after the release of the therapeutic molecules. But animal tests and clinical trials are still needed before we can put these gold drops in our eyes

This research has received funding from QCAM, the Eye Disease Foundation, the Ministry of Economy and Innovation and the Canadian Instituted of Health Research. Dr Boisselier has been awarded an early-career grant by Fonds de recherche du Québec – Santé. She belongs to the following scientific clusters : QCAM, PROTEO and RRSV.

Bibliography related to this research project:

1. F. Masse, P. Desjardins, M. Ouellette, C. Couture, M.M. Omar, V. Pernet, S.L. Guérin, E. Boisselier (2019) “Synthesis of ultrastable gold nanoparticles as a new drug delivery system” Molecules 24:1-17
2. M. Ouellette*, F. Masse*, G. Lamoureux, E. Boisselier (2019) “Gold nanoparticles in ophthalmology“, Med. Res. Rev. 39(1):302-327
3. M. Ouellette, F. Masse, M. Lefebvre-Demers, Q. Maestracci, P. Grenier, R. Millar, N. Bertrand, M. Prieto, E. Boisselier (2018) “Insights into gold nanoparticles as a mucoadhesive system“, Scientific Reports, 8 : 14357.
4. E. Boisselier, V. Pernet, M. Omar, M. Ouellette, “Ultrastable gold nanoparticles for drug delivery applications and synthesis thereof”, US patent (WO2018102921A1, 2018).

Translated by Matteo Duca, Development and scientific affairs director of QCAM

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