Description du projet
Des nanoparticules pour l’administration efficace de médicaments oculaires
Le traitement des maladies oculaires repose généralement sur des médicaments à base de petites molécules et de protéines, mais il est entravé par une faible absorption. Financé par le programme Actions Marie Skłodowska-Curie, le projet LIPOmRNA entend développer des nanoparticules à base de lipides (LNP pour «lipid-based nanoparticles») afin d’administrer des molécules d’ARNm thérapeutiques dans la cornée et la rétine. Les chercheurs s’attaqueront aux barrières anatomiques et optimiseront la technologie pour l’administration oculaire, en modifiant les LNP avec des caractéristiques sensibles au pH et des propriétés de surface spécifiques à l’œil. L’administration des LNP se fera en recourant à des gouttes ophtalmiques mucoadhésives et à des injections intravitréennes afin d’améliorer la rétention et la perméation. Les résultats du projet permettront de promouvoir la technologie prometteuse de l’ARNm pour le traitement des maladies oculaires.
Objectif
Many severe ocular diseases lead to visual impairment and blindness in millions of patients worldwide, and the number is rapidly growing in aging populations. Most ocular diseases are still without drug treatment and the current treatments are based on the use of small molecules and protein drugs. However, poor ocular absorption and rapid elimination restrict their development and use in ophthalmology.
Technology for mRNA transfer into the cornea and retina and subsequent expression of encoded proteins may open widely applicable possibilities for the treatment of ocular diseases (e.g. various retinal degenerations, uveitis) as topical eye drops or intravitreal injections. However, clinical application of mRNAs is limited by their poor in vivo stability and low cellular entry. Therefore, efficient and safe delivery systems for ocular mRNA transfer are urgently needed.
Our research program aims to develop lipid-based nanoparticle (LNP) systems that are specifically tailored for mRNA delivery into the corneal, conjunctival and retinal cells. The project will address the critical anatomical and physiological barriers of ocular mRNA delivery topically and intravitreally. Chemical structure and composition of LNPs will be carefully modified to optimize mRNA delivery across ocular barriers. Smart pH-sensitive LNPs with eye specific surface moieties will be used to target ocular cells and trigger mRNA release and cytosolic delivery. Moreover, eye drop formulations will be mucoadhesive, increasing precorneal residence time, whereas intravitreal injectables will be capable of permeating in the vitreous and inner limiting membrane into the retinal cells. The representative in vitro and ex vivo test models will be used to select the most promising LNPs for versatile animal experiments. Finally, in vivo pharmacokinetics and mRNA mediated anti-VEGF responses of the delivery systems will be investigated to understand their translational potential towards clinical use.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
70211 KUOPIO
Finlande