Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease. (June 2017)

• Record Type: Journal Article
• Authors: Lee, David; Lu, Qiaozhi; Sommerfeld, Sven D.; Chan, Amanda; Menon, Nikhil G.; Schmidt, Tannin A.; Elisseeff, Jennifer H.; Singh, Anirudha
• Is Part Of: Acta biomaterialia. Volume 55(2017)
• Page Start: 163
• Page End: 171
• Publication Date: 2017-06
• Subjects: Hyaluronic acid -- Eye drops -- Peptides -- Sialic acid -- Dry eye; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2017.03.043
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: 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. Statement of Significance: 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.