Biologic drugs are washed out very efficiently from wet epithelia, which prevents their therapeutic effects. University of Pittsburgh researchers have developed a novel approach to deliver biological or other drugs to wet epithelia. Using “anchor domains”, therapeutic agents can be attached to epithelial surfaces, significantly extending exposure time Given the variety of wet epithelia in the body, this technology could have applications in fields as diverse as ophthalmology, rheumatology, gynecology, and respiratory health.
Description
Biological treatments (e.g., monoclonal antibodies) are commonly used to treat inflammation and are increasingly used in numerous fields of medicine. Currently, most biologics are administered systemically, increasing the risk of adverse events. Direct application areas of concern would benefit patient care. Wet epithelia (e.g., eyes), while being accessible for topical drug delivery, are highly efficient at removing foreign substances (e.g., tear film and blinking), clearing any topically applied treatment in 2-3 minutes. Anchor domains have been identified and can bind to the surface of the eye. These anchor domains can be attached to biologic or other therapeutic agents holding them in place and resisting washout. Ultimately this approach can be used to treat inflammation on wet epithelia directly eliminating the need for systemic treatment, reducing side effects, and allowing more targeted treatments.
Applications
• Corneal inflammation
• Periodontal disease
• Respiratory diseases including chronic obstructive pulmonary disease and asthma
• Autoimmune diseases including donor organ rejection and rheumatoid arthritis
• Gynecological conditions including atrophic vaginitis
Advantages
Inflammation at the ocular surface (e.g., dry eye) is a common eye complaint and is typically treated with steroids applied topically in the form of eye drops. However, steroids can induce blinding diseases, cataracts, or glaucoma, and are not recommended for long-term use. Biologic therapies could provide safer treatment options for corneal inflammation, but due to rapid washout from the surface of the eye, none are currently used.
Two anchor domains derived from bovine von Willebrand Factor (vWF) and lectin wheat germ agglutinin (WGA) can bind to wounded surfaces of the eye and resist washout. These domains can be readily attached to therapeutic peptides or proteins extending residency time and could be used with virtually any antibody to target various mucosal tissues directly.
Invention Readiness
In an animal model of dry eye, WGA was attached to an IL-17A antibody labelled with a fluorescent tag (WGA-IL17A) and applied directly to the ocular surface. Compared to the free antibody, which was cleared within 2-3 minutes after application, retention of WGA-IL17A had a 350 fold increased half-life of clearance and could still be detected after 24 h. WGA-IL17A was found to treat dry eye when applied daily. Other anchored antibodies could also effectively treat dry eye with no toxicity observed.
IP Status
https://patents.google.com/patent/US11529389B2
