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Improving treatment options and outcomes in fungal keratitis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41EY030384-01
Agency Tracking Number: R41EY030384
Amount: $149,995.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: N
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-30
Award End Date (Contract End Date): 2020-09-29
Small Business Information
University, MS 38677
United States
DUNS: 081099369
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (662) 915-3793
Business Contact
Phone: (816) 820-2797
Research Institution
UNIVERSITY, MS 38677-0907
United States

 Nonprofit college or university

ABSTRACT Fungal keratitisprimarily caused by CandidaFusariumor Aspergillus speciesis a leading cause of blindness among corneal diseasesAmphotericin BAmBremains the gold standard in the treatment of Candida keratitis and is also the fallback option for other corneal fungal infectionsAlthough widely used off label in ocular infectionsophthalmic AmB formulations are not available commerciallyThe compounded formulations usedreconstituted AmB for injectionare not optimized for ocular administration and suffer from several deficienciese gstability of reconstituted solutionanionic surfactant concentrationsthat limit effective use of AmB in fungal infections of the eyeThis application is based on the hypothesis that novel AmB loaded nanostructured lipid carriersusing castor oil as the liquid lipid and modified with PEG of specific molecular weightsPEG NLC AmBwill provide a stablelong acting and effective multidose ophthalmic formulationThe hypothesis is strongly supported by the preliminary data that demonstrates that these specific PEG NLC AmB formulations are stable on reconstitutionautoclavableand more potent in vitro against Candida albicans and Aspergillus fumigatus compared to unPEGylated NLCs and AmBisomeand is equivalent to that ofif not better thanFungizoneMoreoveraddition of a preservativebenzalkonium chlorideBACto the PEG NLC AmB formulation did not cause any apparent change in the particle sizepolydispersity index or in vitro activitywhereasagglomeration precipitation and inconsistent in vitro activity was observed with the two reconstituted commercial formulations in the presence of BACFurthermoreocular bioavailability of AmB from PEG NLC AMB formulationsfollowing topical instillationwas equivalent to that obtained with AmBisomeThe objective of this Phase I application is to optimize the promising formulation leadsincluding surface modified and in situ gelling formulationsand to evaluate in vivo efficacyThe project goals will be met through two specific aimsUnder Aimthe PEG NLC AmB lead formulations will be optimized with respect to process and storage stabilitylyophilized as well as post reconstitutionformulation characteristicspreservative compatibilitycorneal permeabilitycytotoxicity and in vitro fungicidal activityThe best two formulations will proceed to Aimto test the efficacy against Candida keratitis in the New Zealand white rabbitsCompounded AmB formulations will serve as the control formulationOnly one eye of each rabbit will be infected but the formulation will be administered to both eyesEfficacy will be evaluated at two dosesandmg mLof each of the formulationsThe infected eye of each rabbit will be examinedand clinical disease severity scores will be assignedThe uninfected eye will be assessed for irritation using the Draize numerical scoring system to assess safety of the formulationsAll animal studies will be undertaken under approved protocolsSuccessful development of the PEG NLC AmB ophthalmic formulation will provide a much needed affordableeffective and safe option for treating and managing fungal keratitis and other ocularuveal retinalmucosaltopical and or systemic fungal infections Project Narrative Fungal infections of the eye pose a serious threat globally and can lead to blindnessAlthough Amphotericin B is still one of the most effective antifungal agents and is widely used off label by physicians to treat ocular fungal infectionsFDA approved ophthalmic formulations are not availableThe overall objective of this application is to close this gap by developing a safeeffective and affordable ophthalmic Amphotericin B formulation for the treatment and management of fungal keratitis

* Information listed above is at the time of submission. *

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