Intranasally Administered Nanoparticles Reach the Retina and Choroid in Mice

Purpose : Intranasal delivery of nanoparticle-based systems has been explored in the treatment of central nervous system disorders like Alzheimer's Disease and Parkinson'sDisease given the intranasal route's unique ability to bypass the blood-brain barrier todirectly deliver the rapeutics to the brain and nanoparticle-based systems' ability to overcome the nose's mucocilliary clearance and epithelial barrier challenges. Wehypothesize that intranasally delivered nanoparticles will similarly bypass the blood-retinabarrier to reach the retina and choroid. Methods : 24 male C57Bl/6J mice (Jackson Labs) were given 10ul of suspended fluorescent-labeled polystyrene (PS) nanoparticles (PS-NP) (2mg/ml) into each nostril (20ul total). The type of nanoparticles given was based on the mice's treatment group (n=4 mice pergroup). There were six treatment groups consisting of PS-NPs (FluoSpheresTM) of 3 sizes(40nm, 100nm, 200nm) with and without PEGylation. After anesthesia with intraperitonealEuthasol and euthanasia by cardiac perfusion (PBS with heparin and 4% PFA), the bottomjaw was removed as well as skin, except around the nose. After removing the top of the skull, tissue was cut at 100um on a cryostat. The presence of fluorescent-labeled PS-NP was examined in cryosections of the head and whole eye, using confocal microscopy. Results : 30 minutes after intranasal administration of fluorescent-labeled PS-NP, fluorescent signal was evident in ocular tissue in all six treatment groups. Fluorescentpatterning indicated deposition of nanoparticles in all layers of the retina from the nervefiber layer to the photoreceptor outer segments, as well as the retinal pigment epithelium and the choroid. Sections of the nasal passages and olfactory bulb also indicateddeposition of intranasal nanoparticles in these areas. Conclusions : To the best of our knowledge, this is the first study to demonstrate thatnanoparticles of varying sizes (40nm, 100nm, 200nm), with and without PEGylation aredelivered intranasally to the retina and choroid within 30 minutes of administration. The sedata suggest that intranasal nanoparticle-based drug delivery systems may potentially beused to deliver different types of medications to the retina and choroid in the future. Thismay revolutionize the field of retinal pharmacotherapeutics in diverse retinal disordersincluding diabetic macular edema and exudative age-related macular degeneration.