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Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice

Authors :
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
Source :
Pharmaceutics, Vol 13, Iss 10, p 1650 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

Language :
English
ISSN :
19994923
Volume :
13
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.fef7fae1b1475e9c5cd6030b0df436
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics13101650