Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat...

Area of Science:

• Nanotechnology
• Pharmacology
• Radiochemistry

Background:

• Developing effective methods for drug delivery to the brain is crucial.
• Nose-to-brain delivery offers a potential non-invasive route for therapeutic agents.
• Radiolabeled nanoparticles can be tracked in vivo for pharmacokinetic studies.

Purpose of the Study:

• To develop and validate a quantitative protocol for tracking intranasal aerosolized radiolabeled polymeric micellar nanoparticles (LPNPs).
• To assess the nose-to-brain delivery efficiency of LPNPs compared to intravenous administration in a rat model.
• To establish an in vivo imaging method for evaluating new radio-nanotheranostic agents.

Main Methods:

• Polymeric micellar nanoparticles (LPNPs) were labeled with ⁸⁹Zr PET tracer.
• LPNPs were administered intranasally via aerosol or intravenously in rats.
• Serial PET/CT imaging was performed, followed by ex vivo biodistribution studies of brain substructures.

Main Results:

• Intranasal delivery of ⁸⁹Zr-LPNPs resulted in increased brain activity compared to intravenous administration at 1 and 2 hours post-delivery.
• PET/CT imaging results correlated well with ex vivo gamma counting and autoradiography.
• The study established a temporal and spatial profile of LPNP distribution in the brain.

Conclusions:

• Aerosolized intranasal delivery of LPNPs is a viable strategy for enhancing nose-to-brain drug delivery.
• The presented protocol provides a platform for evaluating nanotheranostic agents targeting the olfactory epithelium.
• Further development is needed to overcome limitations in current nose-to-brain delivery technology.