Lipid Nanoparticles Targeting the Brain Through Intranasal Delivery

Presenter: Vy Nguyen Khanh Do

Faculty Sponsor: Jingjing Gao

School: UMass Amherst

Research Area: Engineering

Session: Poster Session 6, 4:15 PM - 5:00 PM, Auditorium, A15

ABSTRACT

Despite the rising prevalence of brain disorders, achieving precise drug delivery to the brain remains challenging. The brain is protected by the highly restrictive blood-brain barrier (BBB), which resists drug penetration into the brain following systemic administration. Immune responses further reduce the drug’s half-life, limiting its ability to reach the brain before clearance. Fortunately, nose-to-brain delivery offers a direct and non-invasive pathway to the central nervous system, bypassing systemic circulation and the limitations of the BBB. This alternate approach has gained significant attention for advancing brain therapies. Moreover, incorporating nanoscale drug delivery systems enhances intranasal cargo transport by providing protection, facilitating uptake, improving targeting, and reducing side effects. In this study, we develop lipid nanoparticle (LNP) formulations that are optimized for intranasal delivery, emphasizing the olfactory region as a direct route to the brain. By utilizing a DNA barcoding system, more than 150 formulations with varying lipid compositions are evaluated to identify the most efficient candidates that can interact with the nasal mucosa and facilitate brain penetration. The accumulation and biodistribution of each formulation are observed and analyzed thoroughly. To improve targeting accuracy, an administration model using a catheter to reach the upper olfactory region of the nasal cavity is used to validate the performance of top formulations. The success of this project will provide a universal delivery platform through the nasal route for nucleic acid therapeutics, offering promising solutions for treating neurodegenerative diseases.

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