Cell-Penetrating Peptide-Modified PLGA Nanoparticles for Enhanced Nose-to-Brain Macromolecular Delivery

Macromolecular drugs become an essential part in neuroprotective treatment. However, the nature of ineffective delivery crossing the blood brain barrier (BBB) renders those macromolecules undruggable for clinical practice. Recently, brain target via intranasal delivery have provided a promising solution to circumventing the BBB. Despite the direct route from nose to brain (i.e. olfactory pathway), there still are big challenges for large compounds like proteins to overcome the multiple delivery barriers such as nasal mucosa penetration, intracellular transport along the olfactory neuron, and diffusion across the heterogeneous brain compartments. Herein presented is an intranasal strategy mediated by cell-penetrating peptide modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the delivery of insulin to the brain, a potent therapeutic against Alzheimer's disease. The results revealed that the cell-penetrating peptide can potentially deliver insulin into brain via the nasal route, showing a total brain delivery efficiency of 6%. It could serve as a potential treatment for neurodegenerative diseases.