title: Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.
abstract: Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.
authors.affiliation: Department of Chemical Engineering, University of Waterloo , Waterloo, Canada.|Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.
authors.forename: Shengyan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Chemical Engineering, University of Waterloo , Waterloo, Canada.|Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Dozois
authors.affiliation: Department of Chemical Engineering, University of Waterloo , Waterloo, Canada.|Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.
authors.forename: Chu Ning
authors.initials: CN
authors.lastname: Chang
authors.affiliation: Department of Chemical Engineering, University of Waterloo , Waterloo, Canada.|Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.
authors.forename: Aaminah
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Chemical Engineering, University of Waterloo , Waterloo, Canada.|Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.
authors.forename: Deborah L T
authors.initials: DL
authors.lastname: Ng
authors.affiliation: Centre for Contact Lens Research, School of Optometry and Vision Science, University of Waterloo , Waterloo, Canada.
authors.forename: Denise
authors.initials: D
authors.lastname: Hileeto
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital , Toronto, Canada.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Liang
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital , Toronto, Canada.
authors.forename: Matthew-Mina
authors.initials: MM
authors.lastname: Reyad
authors.affiliation: Keenan Research Centre for Biomedical Science, St. Michael's Hospital , Toronto, Canada.
authors.forename: Shelley
authors.initials: S
authors.lastname: Boyd
authors.affiliation: Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.|Centre for Contact Lens Research, School of Optometry and Vision Science, University of Waterloo , Waterloo, Canada.
authors.forename: Lyndon W
authors.initials: LW
authors.lastname: Jones
authors.affiliation: Department of Chemical Engineering, University of Waterloo , Waterloo, Canada.|Waterloo Institute of Nanotechnology, University of Waterloo , Waterloo, Canada.
authors.forename: Frank X
authors.initials: FX
authors.lastname: Gu
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000737:chemistry; D016572:Cyclosporine / Q000737:chemistry / Q000627:therapeutic use; D015352:Dry Eye Syndromes / Q000188:drug therapy*; D005128:Eye Diseases / Q000188:drug therapy*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D011817:Rabbits
chemical_list: D001897:Boronic Acids; D009883:Ophthalmic Solutions; D016572:Cyclosporine; D019158:N-Acetylneuraminic Acid; C010686:benzeneboronic acid
keywords: drug delivery; dry eye; mucoadhesive nanoparticles; ocular retention; phenylboronic acid