SCDT-20. NEW THERAPEUTIC APPROACH FOR BRAINSTEM GLIOMA: INTRANASAL DELIVERY OF NANOLIPOSOMAL SN-38

Abstract

INTRODUCTION

Children with diffuse intrinsic pontine gliomas (DIPGs) die within 2 years after initial diagnosis. The infiltrative nature and anatomic location of DIPGs in an eloquent area of the brain preclude surgical resection, and the blood-brain barrier (BBB) reduces the availability of systemically administered agents. In order to improve outcomes for patients with DIPG, new drug delivery approach circumventing the BBB are greatly needed. Intranasal delivery (IND) is a practical, noninvasive method to deliver therapeutic agents into the brain along with the olfactory and trigeminal nerves pathway. With the advantages of reducing systemic side effects and convenient self-administration for patients, IND is an alternative to systemic (intravenous) and/ or direct invasive (intraparechymal) drug delivery.

METHODS

Two human DIPG cell lines were treated with hydrophobic fluorophore (DiI)-labeled nanoparticle liposomes containing CPT-11 (nanoliposomal CPT-11) and SN-38. Cell viability was determined by MTS assay and intracellular localization was imaged by confocal microscopy. For in vivo study, mice bearing human brainstem gliomas were randomly assigned to 3 groups: 1. empty nanoliposomes, 2. nanoliposomal CPT-11, 3. nanoliposomal SN-38, administrating by IND for 3 weeks. In vivo distribution was determined by DiI-labeled nanoliposomal SN-38 into the tumor bearing mice. Tumor growth and response to therapy were quantitatively measured by bioluminescence imaging, and efficacy was assessed by survival analysis.

RESULTS

DiI-fluorescence were detected at 30 minutes and peaked at 24 hours following treatment with DiI nanoliposomal SN-38. Nanoliposomal SN-38 induced dose dependent inhibition of the growth of DIPG cells, that is greater inhibition than nanoliposomal CPT-11. IND of nanoliposomal SN-38 showed significant reduction of the growth rate in compared to IND of empty nanoliposome. Results from animal survival will be reported at the meeting.

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