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Delivery to the Nervous System

(155) In-Vivo Study on Nose-to-Brain Delivery of Liposomal siRNA/Drug Combination for Alzheimer’s Disease

Introduction: Challenges for treating Alzheimer's Disease (AD) include crossing of the blood-brain-barrier (BBB), aggregation of amyloid beta (Aβ) protein in the brain, and the lack of potency with traditional delivery forms. We have designed a liposomal formulation that can be administered via the intranasal route, which provides advantages of bypassing the BBB and delivering large therapeutic payloads with limited off-target effects [1]. Herein, we have demonstrated the safety and efficacy of a triple-drug liposomal therapy comprised of BACE-1 siRNA, donepezil, and memantine to transgenic APP/PS1 mice.

Learning Objectives:

  • Demonstrate the increased efficacy of a triple-drug siRNA liposomal therapy via nose-to-brain
  • Evaluate the enhanced pharmacological effects of nose-to-brain delivery through AD mouse model.
  • Explain the mechanistic advantages of liposomal formulations administered intranasally.