Descripción del proyecto
Nanopartículas para una administración oftálmica de fármacos eficaz
El tratamiento de las enfermedades oculares se suele basar en fármacos de bajo peso molecular y fármacos proteicos, pero su eficacia se ve limitada por su baja absorción. En el proyecto LIPOmRNA, financiado por las acciones Marie Skłodowska-Curie, se pretende desarrollar nanopartículas lipídicas (NPL) para administrar moléculas terapéuticas de ARN mensajero (ARNm) en la córnea y la retina. Sus investigadores abordarán las barreras anatómicas y optimizarán la tecnología para la administración por vía oftálmica, modificando las NPL con características sensibles al pH y propiedades superficiales específicas para los ojos. La administración de las NPL se efectuará con colirios mucoadhesivos e inyectables intravítreos, a fin de mejorar la retención y la permeación de las mismas. Los resultados del proyecto incentivarán la prometedora tecnología del ARNm para el tratamiento de enfermedades oculares.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinador
70211 KUOPIO
Finlandia