TSRL, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

Abstract Yearly influenza epidemics strike millions of peoplecausing up todeathsFatality caused by most seasonal influenza viruses is ltbut with significant mortality in the young and the elderly populationsWhen a new pathogenic influenza strain enters the populationa pandemic could kill tens of millions of people with a negative economic impact estimated to be overbillion dollarsInfluenza virus is a NIAID category C priority biothreatcharacterized as an emerging agent that is readily available and disseminatedDue to the incomplete efficacy of the current vaccineseffective drug treatment is necessaryPresentlyinfluenza treatment is only somewhat effectiveand some influenza strains are resistant to the currently marketed therapeuticsadamantanes and the neuraminidase inhibitor TamifluHoweverzanamivirRelenzaremains highly active against oseltamivir resistant influenza strainsbut its therapeutic impact is severely limited by its route of administrationvia oral inhalationwhich renders it unsuitable for patients with a compromised respiratory systemThereforedevelopment of a novel delivery alternative for zanamivir as we propose hereis poised to address a significant unmet medical needApplication of a transdermal microneedle delivery strategy to the anti viraland particularly anti influenzamarket offers a number of solutions to large unmet medical needsand represents an attractive market entry strategyTransdermal delivery systems offer a number of improvements over other delivery systemsPatches do not require swallowingeliminating oral side effectsPermeation through the skin allows the drug to directly enter the systemic circulation and avoid any absorption and first pass barriers a drug might encounter with oral deliveryFinallytransdermal delivery avoids skin puncture by syringe needleseliminating pain and patient visits to a physicianTransdermal delivery of ZAN is desirable during an influenza outbreakas large numbers of patients can be reachedThe Phase I portion of this proposal will involve formulation optimization of the prototype patch and subsequent pharmacokinetic and efficacy testing in miceThe final study for this proposal will be a dermatotoxicology studies to assess skin irritation of the final patches in rabbitsThe end result of this work will be a noveltransdermal delivery approach for zanamivir with demonstrated efficacyPK and initial preclinical safety data ready to complete preclinical development activities leading to the opening of an INDWe have assembled a team of expert advisors and collaborators to ensure successful completion of this research plan