Abstract
AbstractBiologics are almost exclusively administered systemically, but localized delivery is preferable as it minimizes off-target exposure and allows more aggressive treatments. Topical application of biologics to epithelia is generally ineffective because most are covered with fluids and biologics are washed out too quickly to have significant therapeutic effects. Here we explore the idea that attaching a binding domain can serve as an “anchor” to extend the residency time of biologics on wet epithelia, allowing their effective use even with infrequent applications. We use topical application to the ocular surface as a challenging test since foreign substances are washed out especially efficiently by tear flow and blinking. Our results demonstrate that conjugation of antibodies to wheat germ agglutinin, which binds GlcNAc and sialic acid that are ubiquitously present in tissues, increases their half-life 350-fold upon application to the ocular surface in a mouse model of dry eye, a common and onerous disease in humans. Importantly, antibodies to IL-17A, IL-23, and IL-1β conjugated to the agglutinin reduces manifestations of dry eye, even when applied just once daily. In contrast, unconjugated antibodies are ineffective. Attaching an anchor to biologics is a simple means to overcome washout and to extend their therapeutic use.
Funder
Pitt | Clinical and Translational Science Institute, University of Pittsburgh
National Science Foundation
Eye and Ear Foundation of Pittsburgh
Research to Prevent Blindness
U.S. Department of Health & Human Services | NIH | National Eye Institute
Sjogren’s Syndrome Foundation, Lions Club of eastern Pennsylvania, Bruce and Barbara Wiegand Family Foundation, Chancellor’s Award, University of Pittsburgh.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Cited by
1 articles.
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