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Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus
Eugene P Chung1,2, Jennifer D Cotter3, Alesia V Prakapenka1,2
1Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
Pharmaceutics
|January 30, 2020
Summary
Intranasal delivery of polymer nanoparticles effectively bypasses the blood-brain barrier for central nervous system drug delivery. Surface modification with RVG29 enhances nanoparticle transport via the trigeminal nerve, improving drug delivery to the brain.
Area of Science:
- Neuroscience
- Nanotechnology
- Pharmacology
Background:
- The blood-brain barrier (BBB) limits effective drug delivery to the central nervous system (CNS).
- Alternative administration routes, such as intranasal delivery, offer potential to bypass the BBB.
- Polymer nanoparticles (PLGA) are investigated for CNS drug delivery applications.
Purpose of the Study:
- To evaluate the efficacy of intranasal delivery of PLGA nanoparticles for CNS drug delivery.
- To investigate the impact of RVG29 surface modification on nanoparticle residence time and CNS exposure.
- To elucidate the mechanisms of nose-to-brain drug delivery.
Main Methods:
- PLGA nanoparticles loaded with DiR dye were administered intranasally to healthy mice.
- Surface modification with RVG29 was used to target nanoparticles.
- Delivery kinetics and biodistribution were analyzed in various organs and CNS regions.
- Trigeminal nerve and olfactory routes were investigated as potential transport pathways.
Main Results:
- Intranasal administration resulted in rapid and effective delivery to the whole brain with minimal peripheral organ exposure.
- Higher payload delivery was observed in CNS tissues near the trigeminal nerve.
- RVG29-modified nanoparticles showed modest targeting benefits in specific brain regions at 2 hours post-administration.
- Payload delivery to the trigeminal nerve was significantly higher for targeted nanoparticles.
Conclusions:
- Intranasal administration of PLGA nanoparticles is a viable strategy for nose-to-brain drug delivery.
- The trigeminal nerve plays a crucial role in nanoparticle transport from the nasal cavity to the CNS.
- Surface modification can enhance nanoparticle targeting, supporting the development of effective CNS drug delivery vectors.

