DECON: A sustained topical delivery platform to treat ocular inflammation

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Ocular inflammatory diseases are the primary cause of blindness in the USA. While emergence of ocular inflammation can be genetic or idiopathic, pathogens such as bacteria, fungi and viruses that infect the eye are primary causes. Microbial infections are treated with antimicrobials followed by anti-inflammatory drugs such as dexamethasone, prednisone, cyclosporine etc. The treatment regimen for these anti-inflammatory drugs is prolonged and can last up to many months or even years. While systemic dosing is often avoided unless necessary, topical dosage regimens can have low patient compliance due to repeated administration requirements per day. One such ailment that affects millions of people around the globe is ocular herpes. Primary infections are usually seen in children or adolescents and associated with vesicular dermatitis, follicular blepharo-conjunctivitis, superficial punctate keratitis (SPKs) or dendritic ulcer with preauricular lymphadenopathy. However, herpesviruses can reside forever in the host latently and cause recurrent ocular infection in patients of all ages. While the most common treatment for treating active ocular herpes infection includes daily dosing of Acyclovir (ACV) or ACV analogs, curbing post viral inflammation, which can cause ocular pain and permanent clouding of the cornea, is performed by topical glucocorticoid treatments such as prednisone or dexamethasone. These topical glucocorticoid therapies are avoided during active viral replication and only prescribed in conjunction with oral antivirals to avoid the risk of involving deeper stromal structures with threats to vision. While topical glucocorticoid treatments are effective in reducing inflammation in most cases, they require repeated dosing (6-10 times daily) and suffer from poor ocular retention. A simple yet effective way to improve ocular retention time for topical therapies is to use sustained drug release platforms. We have recently shown that ACV loaded into highly porous activated carbon termed as drug encapsulated carbon (DECON), can effectively adsorb to the corneal surface and deliver drug in a sustained fashion. We showed that use of DECON to deliver ACV, reduced the dosage frequency from 3 in a single day to a single dose once every alternate day in mice. In this regard, we propose to demonstrate a new use for DECON as a sustained drug release platform to deliver dexamethasone during post viral inflammation period. In this proposal, we would like to (1) understand the efficacy of drug loading, retention and release of dexamethasone from DECON using in vitro, ex vivo and in vivo models and (2) through clinically relevant metrics assess DECON’s ability to reduce infectious and non-infectious suppress inflammation during post viral replication period.