title: Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease.
abstract: Hyaluronic acid (HA) solutions effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms. However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation. Conversely, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Here, we developed an HA-eye drop formulation that selectively binds and retains HA for extended periods of time on the ocular surface. We synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binding either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. HA solution was mixed with the polymer-peptide system and tested on both ex vivo and in vivo models to determine its ability to prolong HA retention. Furthermore, rabbit ocular surface tissues treated with binding peptides and HA solutions demonstrated superior lubrication with reduced kinetic friction coefficients compared to tissues treated with conventional HA solution. The results suggest that binding peptide-based solution can keep the ocular surface enriched with HA for prolonged times as well as keep it lubricated. Therefore, this system can be further developed into a more effective treatment for dry eye patients than a standard HA eye drop.
  
  
  
  Eye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a standard HA eye drop.
authors.affiliation: Translational Tissue Engineering Center, Department of Biomedical Engineering and Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: Translational Tissue Engineering Center, Department of Biomedical Engineering and Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Materials Science & Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Qiaozhi
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Translational Tissue Engineering Center, Department of Biomedical Engineering and Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Sven D
authors.initials: SD
authors.lastname: Sommerfeld
authors.affiliation: Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Chan
authors.affiliation: Department of Materials Science & Engineering, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Nikhil G
authors.initials: NG
authors.lastname: Menon
authors.affiliation: Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada; Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.
authors.forename: Tannin A
authors.initials: TA
authors.lastname: Schmidt
authors.affiliation: Translational Tissue Engineering Center, Department of Biomedical Engineering and Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
authors.affiliation: Translational Tissue Engineering Center, Department of Biomedical Engineering and Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Urology and Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA. Electronic address: asingh29@jhu.edu.
authors.forename: Anirudha
authors.initials: A
authors.lastname: Singh
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D010455:Peptides; D006820:Hyaluronic Acid
keywords: Dry eye; Eye drops; Hyaluronic acid; Peptides; Sialic acid