Functionalization of Morin-Loaded PLGA Nanoparticles with Phenylalanine Dipeptide Targeting the Brain
Mario Alonso,
Emilia Barcia,
Juan-Francisco González,
Consuelo Montejo,
Luis García-García,
Mónica-Carolina Villa-Hermosilla,
Sofía Negro,
Ana-Isabel Fraguas-Sánchez,
Ana Fernández-Carballido
Affiliations
Mario Alonso
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Emilia Barcia
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Juan-Francisco González
Department of Chemistry in Pharmaceutical Sciences, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Consuelo Montejo
Department of Health and Pharmaceutical Sciences, School of Pharmacy, Universidad San Pablo-CEU, 28668 Boadilla del Monte, Spain
Luis García-García
Department of Pharmacology, Pharmacognosy and Botany, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Mónica-Carolina Villa-Hermosilla
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Sofía Negro
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Ana-Isabel Fraguas-Sánchez
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Ana Fernández-Carballido
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, 28040 Madrid, Spain
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, with its incidence constantly increasing. To date, there is no cure for the disease, with a need for new and effective treatments. Morin hydrate (MH) is a naturally occurring flavonoid of the Moraceae family with antioxidant and anti-inflammatory properties; however, the blood–brain barrier (BBB) prevents this flavonoid from reaching the CNS when aiming to potentially treat AD. Seeking to use the LAT-1 transporter present in the BBB, a nanoparticle (NPs) formulation loaded with MH and functionalized with phenylalanine-phenylalanine dipeptide was developed (NPphe-MH) and compared to non-functionalized NPs (NP-MH). In addition, two formulations were prepared using rhodamine B (Rh-B) as a fluorescent dye (NPphe-Rh and NP-Rh) to study their biodistribution and ability to cross the BBB. Functionalization of PLGA NPs resulted in high encapsulation efficiencies for both MH and Rh-B. Studies conducted in Wistar rats showed that the presence of phenylalanine dipeptide in the NPs modified their biodistribution profiles, making them more attractive for both liver and lungs, whereas non-functionalized NPs were predominantly distributed to the spleen. Formulation NPphe-Rh remained in the brain for at least 2 h after administration.