Nanoparticle transport across in vitro olfactory cell monolayers

Area of Science:

• Neuroscience
• Nanotechnology
• Pharmacology

Background:

• The blood-brain barrier (BBB) restricts drug entry into the central nervous system (CNS).
• Intranasal drug delivery offers a non-invasive route for direct nose-to-brain transport, bypassing the BBB.
• Nanoparticles (NPs) are effective carriers for nose-to-brain drug delivery, but their transport mechanisms require further investigation.

Purpose of the Study:

• To develop and validate in vitro olfactory cell monolayers for studying nose-to-brain transport.
• To investigate the transport of polymeric and lipid-based NPs across these monolayers.
• To evaluate the role of cell-penetrating peptides (CPPs) in enhancing NP brain uptake.

Main Methods:

• Development and characterization of poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) NPs.
• Validation of in vitro olfactory cell monolayers as a model for BBB transport.
• Assessment of NP transport across cell monolayers with and without CPPs (Tat and Penetratin).

Main Results:

• PLGA NPs showed minimal transport (0.7%) across olfactory cell monolayers.
• NLCs demonstrated significantly higher transport (8%), with chitosan-coated NLCs (CS-NLCs) showing 22% transport.
• Incorporation of CPPs onto CS-NLCs dramatically increased transport to 46%.

Conclusions:

• CPP-modified CS-NLCs are highly effective for nose-to-brain drug delivery.
• This study validates an in vitro model for assessing NP brain transport via the intranasal route.
• CPP-CS-NLCs represent a promising strategy for targeted CNS drug delivery, overcoming BBB limitations.