Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice
Marco Bassetto,
Daniel Ajoy,
Florent Poulhes,
Cathy Obringer,
Aurelie Walter,
Nadia Messadeq,
Amir Sadeghi,
Jooseppi Puranen,
Marika Ruponen,
Mikko Kettunen,
Elisa Toropainen,
Arto Urtti,
Hélène Dollfus,
Olivier Zelphati,
Vincent Marion
Affiliations
Marco Bassetto
OZ Biosciences, Parc Scientifique de Luminy, Case 922, Zone Entreprise, CEDEX 9, 13288 Marseille, France
Daniel Ajoy
INSERM, Ciliopathies Modeling and Associated Therapies Group, Laboratoire de Génétique Médicale, UMRS_U1112, Fédération de Médicine Translationelle de Strasbourg, Université de Strasbourg, 67085 Strasbourg, France
Florent Poulhes
OZ Biosciences, Parc Scientifique de Luminy, Case 922, Zone Entreprise, CEDEX 9, 13288 Marseille, France
Cathy Obringer
INSERM, Ciliopathies Modeling and Associated Therapies Group, Laboratoire de Génétique Médicale, UMRS_U1112, Fédération de Médicine Translationelle de Strasbourg, Université de Strasbourg, 67085 Strasbourg, France
Aurelie Walter
OZ Biosciences, Parc Scientifique de Luminy, Case 922, Zone Entreprise, CEDEX 9, 13288 Marseille, France
Nadia Messadeq
INSERM, Institute of Genetics and Molecular and Cellular Biology (IGBMC), 67640 Illkrich-Graffenstaden, France
Amir Sadeghi
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211 Kuopio, Finland
Jooseppi Puranen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211 Kuopio, Finland
Marika Ruponen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211 Kuopio, Finland
Mikko Kettunen
Kuopio Biomedical Imaging Unit, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70150 Kuopio, Finland
Elisa Toropainen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211 Kuopio, Finland
Arto Urtti
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1C, 70211 Kuopio, Finland
Hélène Dollfus
INSERM, Ciliopathies Modeling and Associated Therapies Group, Laboratoire de Génétique Médicale, UMRS_U1112, Fédération de Médicine Translationelle de Strasbourg, Université de Strasbourg, 67085 Strasbourg, France
Olivier Zelphati
OZ Biosciences, Parc Scientifique de Luminy, Case 922, Zone Entreprise, CEDEX 9, 13288 Marseille, France
Vincent Marion
INSERM, Ciliopathies Modeling and Associated Therapies Group, Laboratoire de Génétique Médicale, UMRS_U1112, Fédération de Médicine Translationelle de Strasbourg, Université de Strasbourg, 67085 Strasbourg, France
Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations. Non-invasive methods of retinal drug targeting are a prerequisite for acceptable adaptation to the targeted pediatric patient population. Here, we present the development and functional testing of a non-invasive, topical, magnetically assisted delivery system, harnessing the ability of magnetic nanoparticles (MNPs) to cargo two drugs (guanabenz and valproic acid) with anti-unfolded protein response (UPR) properties towards the retina. Using magnetic resonance imaging (MRI), we showed the MNPs’ presence in the retina of Bbs wild-type mice, and their photoreceptor localization was validated using transmission electron microscopy (TEM). Subsequent electroretinogram recordings (ERGs) demonstrated that we achieved beneficial biological effects with the magnetically assisted treatment translating the maintained light detection in Bbs−/− mice (KO). To our knowledge, this is the first demonstration of efficient magnetic drug targeting in the photoreceptors in vivo after topical administration. This non-invasive, needle-free technology expands the application of SMDs for the treatment of a vast spectrum of retinal degenerations and other ocular diseases.