ORBIS BIOSCIENCES, INC. — Department of Health and Human Services SBIR Phase I: Y

Description

PROJECT SUMMARY Current approaches to treat sensorineural hearing loss SNHL in newborns suffering from congenital cytomegalovirus CMV infection rely on off label systemic antiviral therapy requiring high dose long duration treatment with demonstrated hematologic toxicity carcinogenicity and teratogenicity Furthermore it is unknown whether systemic delivery of antivirals maintain inner ear drug concentrations within an appropriate therapeutic window for sufficient lengths of time to achieve therapeutic effect A novel delivery system for long term controlled release of antivirals to the inner ear would constitute a dramatic improvement in CMV related SNHL treatment options Our proposed strategy uses Unisun technology to create a long acting single transtympanic injection of ganciclovir loaded microspheres for round window membrane RWM localization and sustained release to the inner ear The central advantage of our approach is that Unisun allows for precise control of particle size shape material and drug release rates Our long term goal is for transtympanic delivery of Unisun enabled ganciclovir loaded microspheres to be the standard of care for newborns suffering from CMV related SNHL We hypothesize that microspheres can be retained on the RWM for over four weeks and that ganciclovir release can be maintained g day to sustain a therapeutic concentration in the inner ear fluid We expect that this novel approach to localize ganciclovir treatment to the inner ear will dramatically improve the safety and efficacy of antiviral therapy for CMV related SNHL over current non FDA approved options Orbis research team will first develop and characterize the relationship between the microsphere size material drug concentration and ganciclovir release profiles to establish the feasibility of achieving long term controlled release to the inner ear Aim We will then determine the optimal microsphere immobilization strategy to enable RWM localization for a minimum of one month with minimal toxicity in a guinea pig model Aim This Unisun enabled drug delivery strategy addresses issues of dosage accuracy and long term release In addition Unisun based encapsulation is highly adaptable and can serve as a transtympanic delivery platform for multiple drug classes This unique strategy has significant potential to become the standard of care for treatment of CMV related SNHL PROJECT NARRATIVE Current approaches to treat sensorineural hearing loss SNHL in newborns suffering from congenital cytomegalovirus CMV infection rely on off label oral or intravenous antiviral therapy requiring high doses and long dosing regimens of molecules with known hematologic toxicity carcinogenicity and teratogenicity A novel localized delivery system for long term controlled release of antivirals such as ganciclovir to the site of infection in the inner ear would constitute a dramatic improvement over existing CMV induced SNHL treatment options by considerably decreasing the required dose and simplifying the dosing regimen into a single long acting injection Our proposed strategy uses Unisun technology to engineer a transtympanic injection of ganciclovir loaded microspheres that are designed to remain affixed to the round window membrane of the inner ear and provide localized controlled and sustained release of the therapeutic throughout the treatment period