Descrizione del progetto
Un’efficace somministrazione di farmaci per via oculare grazie alle nanoparticelle
Il trattamento delle malattie che colpiscono gli occhi si basa spesso su farmaci a base di piccole molecole e proteine che, tuttavia, hanno un basso livello di assorbimento per via oculare. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto LIPOmRNA mira a sviluppare nanoparticelle a base lipidica allo scopo di veicolare molecole di mRNA terapeutico nella cornea e nella retina. I ricercatori affronteranno le barriere anatomiche e ottimizzeranno la tecnologia per la somministrazione oculare modificando queste nanoparticelle con caratteristiche sensibili al pH e proprietà di superficie specifiche per gli occhi. Per migliorare la ritenzione e la permeazione, la somministrazione delle nanoparticelle a base lipidica avverrà attraverso formulazioni di colliri mucoadesivi e iniettabili intravitreali. I risultati del progetto promuoveranno la promettente tecnologia per il trattamento delle malattie oculari basata sull’mRNA.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
70211 KUOPIO
Finlandia