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Principal Investigator: Tejabhiram Yadavalli
Organization: UNIVERSITY OF ILLINOIS AT CHICAGO
Fiscal Year: 2024
Award: $398,369
Funding agency: National Eye Institute
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.
Terms: <0-11 years old><1, 2-Dehydrocortisone><Acicloftal><Aclovir><Acycloguanosine><Acyclovir><Adolescent><Adolescent Youth><Adrenal Cortex Hormones><Adsorption><Affect><Age><Anti-Inflammatories><Anti-Inflammatory Agents><Anti-inflammatory><Anti-viral Agents><Antiinflammatory Effect><Area><Bacteria><Benzalkonium Chloride><Beta Proprotein Interleukin 1><Blindness><Body Tissues><Carbon><Cargosil><Cell Body><Cells><Characteristics><Child><Child Youth><Children (0-21)><Ciclosporin><Cornea><Corticoids><Corticosteroids><CsA><Cyclosporin A><Cyclosporine><Cyclosporine A><Data><Dehydrocortisone><Delta(1)-Cortisone><Deltacortisone><Deltadehydrocortisone><Dermatitis><Dexamethasone><Dialysis><Dialysis procedure><Disease><Disorder><Dose><Drug Delivery><Drug Delivery Systems><Drug Kinetics><Drug usage><Drugs><Encapsulated><Eye><Eye Development><Eye Drops><Eye Infections><Eye pain><Eyeball><Eyedrops><Formulation><Frequencies><Genetic><Glucocorticoids><Goals><HSV><HSV-1><HSV1><Herpes Simplex><Herpes Simplex Infections><Herpes Simplex Keratitis><Herpes Simplex Type 1><Herpes Simplex Virus><Herpes Simplex Virus 1><Herpes Simplex Virus Type 1><Herpes infection><Herpes labialis Virus><Herpes simplex disease><Herpesviridae><Herpesviridae Infections><Herpesviridae disease><Herpesvirus 1><Herpesvirus Infections><Herpesvirus hominis disease><Herpesviruses><Herpetic Keratitis><Hour><Human><IL-1 beta><IL-1 β><IL-1-b><IL-1β><IL1-Beta><IL1-β><IL1B Protein><IL1F2><IL1β><Implant><In Vitro><Individual><Infection><Inflammation><Inflammatory><Intellectual Property><Interleukin 1beta><Interleukin-1 beta><Interleukin-1β><Keratitis><Knowledge><Legal patent><Light><Mechanics><Medication><Metacortandracin><Mice><Mice Mammals><Modality><Modeling><Modern Man><Murine><Mus><National Eye Institute><Ocular Herpes Simplex><Ocular Herpetic Disease><Ocular Infections><Oral><Paper><Particle Size><Patents><Patient Compliance><Patients><Persons><Pharmaceutical Preparations><Pharmacokinetics><Photoradiation><Physiologic><Physiological><Porosity><Poviral><Prednisone><Prednisonum><Preinterleukin 1 Beta><Primary Infection><Publishing><Recurrence><Recurrent><Regimen><Reporting><Research><Risk><Sampling><Sandimmun><SangCya><Science><Severities><Sight><Simplexvirus><Site><Standardization><Structure><Surface><System><Techniques><Testing><Therapeutic><Time><Tissues><Topical Corticosteroids><Topical Drug Administration><Topical application><Treatment Period><Treatment Protocols><Treatment Regimen><Treatment Schedule><Tube><Ulcer><Ulceration><Universities><Viral><Virorax><Virus><Virus Replication><Vision><Zovirax><adenopathy><administer topically><ages><analog><anti-inflammatory effect><anti-microbial><anti-viral compound><anti-viral drugs><anti-viral medication><anti-viral therapeutic><anti-virals><antimicrobial><apply topically><clinical efficacy><clinical relevance><clinically relevant><common treatment><corneal><corneal herpetic disease><deliver topically><delta-Cortisone><design><designing><determine efficacy><dialysis therapy><dosage><drug efficacy><drug release profile><drug use><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><eye morphogenesis><fungus><herpes simplex i><herpes simplex virus 1 infection><herpes simplex virus infection><herpes simplex virus keratitis><herpes simplex-1><herpes virus><hsv keratitis><improved><in vivo><in vivo Model><juvenile><juvenile human><kids><lymphadenopathy><mechanic><mechanical><microbial><mouse model><murine model><neoral><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><ocular development><ocular herpes><ocular pain><particle><pathogen><patient adherence><patient cooperation><sandimmune><standard of care><topical administration><topical delivery><topical drug application><topical treatment><topically administered><topically applied><topically delivered><topically treated><treat topically><treatment days><treatment duration><viral multiplication><viral replication><virus multiplication><vision loss><visual function><visual loss><youngster>