Functionalization of Morin-Loaded PLGA Nanoparticles with Phenylalanine Dipeptide Targeting the Brain

Area of Science:

• Neuroscience
• Pharmacology
• Biotechnology

Background:

• Alzheimer's disease (AD) is a prevalent neurodegenerative disorder lacking effective treatments.
• Morin hydrate (MH), a flavonoid with antioxidant and anti-inflammatory properties, is hindered from CNS entry by the blood-brain barrier (BBB).
• Targeting the BBB's LAT-1 transporter is a strategy for delivering therapeutics to the brain.

Purpose of the Study:

• To develop and evaluate phenylalanine-functionalized nanoparticles (NPphe-MH) for enhanced BBB penetration and MH delivery.
• To compare the biodistribution and BBB crossing capabilities of functionalized (NPphe-MH) versus non-functionalized nanoparticles (NP-MH).
• To investigate the brain retention of NPphe-MH using rhodamine B (Rh-B) labeled nanoparticles (NPphe-Rh).

Main Methods:

• Formulation of PLGA nanoparticles loaded with MH and functionalized with phenylalanine-phenylalanine dipeptide (NPphe-MH).
• Preparation of non-functionalized nanoparticles (NP-MH) and rhodamine B-labeled counterparts (NPphe-Rh, NP-Rh) for biodistribution studies.
• Administration of nanoparticles to Wistar rats and analysis of biodistribution and brain uptake via fluorescence imaging.

Main Results:

• High encapsulation efficiencies were achieved for MH and Rh-B in PLGA nanoparticles.
• Phenylalanine functionalization altered nanoparticle biodistribution, favoring liver and lung accumulation over spleen.
• NPphe-Rh demonstrated sustained presence in the brain for at least 2 hours post-administration.

Conclusions:

• Phenylalanine-functionalized nanoparticles show promise for improving drug delivery across the BBB.
• NPphe-MH represents a potential strategy for delivering MH to the CNS for Alzheimer's disease treatment.
• Targeted nanoparticle design can overcome biological barriers for effective neurotherapeutics.