495 Optimizing Drug Delivery to the Brain for Breast Metastasis: A Novel Method for Tumor Targeting

INTRODUCTION: Brain metastases are difficult to treat due to the blood-brain barrier limiting delivery of therapeutic agents to the brain effectively. Intraventricular drug delivery has not been well studied for intra-axial pathologies. However, our prior work demonstrated that intraventricular drug delivery in a hyperosmolar vehicle showed preferential accumulation of drug within breast cancer tissue compared to surrounding brain parenchyma. METHODS: We used an intracerebral breast cancer tumor model in adult female nude rats divided into six experimental groups. We examined three iron labeled dextran molecules (3 KD, 5KD, and 10 KD) in 337 mOsm/L solution and three different osmolarities of delivery solution (307, 353, 368 mOsm/L) with 10 KD dextran. 7T MR imaging was used to analyze dextran distribution at different time points. All animals were sacrificed after 2 hours and quantity of dextran particles was determined by histopathology. RESULTS: Breast cancer tumor cells were successfully implanted in all rats. MRI quantification of dextran concentration was well corroborated by histopathology. Varying the molecular size of dextran resulted in the smallest molecule reaching peak levels in tumor tissue earlier than the larger molecules but the larger molecules remained concentrated in tumor tissue for a longer time. Varying the osmolarity of the delivery solution resulted in preferential accumulation of 10 KD dextran in tumor tissue except for when dextran was delivered in 368 mOsm/L solution where no preferential distribution was seen. CONCLUSIONS: Hyperosmolar intraventricular delivery of chemotherapeutic drugs could be effective in preferentially delivering drugs to abnormal tumor tissues.