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Innovative Nose-to-Brain Anticancer Drug Transport Facilitated by NEO100
Phone: (323) 226-7421
Email: tchen68670@usc.edu
Phone: (323) 442-7794
Email: tchen68670@gmail.com
Address:
Type: Nonprofit College or University
Project Summary Abstract Many pharmaceutical agents are highly potentbut are unable to exert substantial therapeutic activity against disorders of the brainbecause the blood brain barrierBBBeffectively prevents their access to the site of intracerebral diseaseFor examplethe majority of glioblastoma patientsdespite the best efforts of current medical caredie within two years after diagnosisHencethere is a great medical need for novel approaches to effective brain drug deliveryin particular for malignant brain cancersbut other diseases as wellAs a solution to this medical needwe seek to develop a novel binary intranasal co delivery method that will circumvent the BBB and enable brain access of otherwise BBB impermeable chemotherapeutic drugsAs a model for a BBB impermeable drugwe chose bortezomibBZMa highly active anticancer compound that is very effective when given intravenously to patients with multiple myelomaa cancer of white blood cellsWe have shown that BZM has the potency to very effectively kill brain cancer cells as wellbut it does not work when given via intravenous infusionbecause it cannot cross the BBB and reach tumors inside the brainPerillyl alcoholPOHis acompound derived from nature that has shown anticancer activity when given via the nose to patients with malignant brain cancerThis delivery method is non invasive and very well toleratedand patients can administer POH themselves with a portable nebulizerIt is thought that the high lipophilicity of POH enables its easy delivery to the brainat least in part via direct nose to brain transportFor our own workwe have uniquely available a highly purified version of POHcalled NEOOur working hypothesis predicts that during intranasal co delivery of NEOand BZMNEOwill act as a nose to brain carrier to transport BMZ into the brainthereby circumventing the BBB obstacleThis wayboth agents will reach the tumor site in the brain and unfold their tumor killing task in concertThe goal of our project is toestablish proof of principle that this intranasal drug co delivery works in a rat tumor modelIn the first specific aimwe will measure how much drug enters the brain of rats after intranasal delivery of BZM in the presence or absence of POHWe will also look for biological markers of drug effectsas an indication that the drugs exerted activityIn the second specific aimwe will use intranasal drug delivery to treat rats with brain cancersin order to determine whether this novel co delivery approach is effective enough to yield therapeutic outcomesIf successfulthis project will set the stage for non invasivebinary nose to brain transport of many other pharmaceutical agents with low BBB penetration activity and potential applicability to diverse CNS disordersIn the case of glioblastomafuture clinical validation and implementation of this approach has the potential to provide an effective therapeutic option to a patient group with otherwise grim prognosis Project Narrative Unlike systemic cancersbrain neoplasms have not benefited from substantial improvements in cancer therapeutic regimens that have occurred over the past decadesMany potent pharmaceutical agents are unable to exert their substantial activities due to the limitation of blood brain barrierBBBAs a solution to this unmet medical needwe seek to develop a novel binary intranasal co deliveryNEOand BZMmethod that will circumvent the BBB and enable brain access of otherwise BBB impermeable chemotherapeutic drugbortezomibBZMSince NEOitself harbors anticancer activityER stress inducerboth agents will reach the tumor foci inside the brain and unfold their tumor killing task in concertIf successfulour project will contribute to the improvement of public health by providing better treatment options for brain tumors
* Information listed above is at the time of submission. *