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. 2022 Oct 31;14(11):2348.
doi: 10.3390/pharmaceutics14112348.

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

Mario Alonso  1 , Emilia Barcia  1   2 , Juan-Francisco González  3 , Consuelo Montejo  4 , Luis García-García  5   6 , Mónica-Carolina Villa-Hermosilla  1 , Sofía Negro  1   2 , Ana-Isabel Fraguas-Sánchez  1   2 , Ana Fernández-Carballido  1   2
Affiliations

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

Mario Alonso et al. Pharmaceutics. .

Abstract

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.

Keywords: Alzheimer’s disease; PLGA; blood–brain barrier; morin hydrate; nanoparticles; rhodamine B.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Reaction scheme for the activation of carboxylic acid groups in PLGA and its functionalization. (B) H1 NMR patterns of PLGA-NHS (upper) and PLGA-phe-phe (lower). NHS: N-hidroxysuccinimide; phe-phe: phenylalanine dipeptide.
Figure 2
Figure 2
SEM images (x20,000) of all NPs formulations. (A) NP-0. (B) NPphe-0. (C) NP-MH. (D) NPphe-MH. (E) NP-Rh. (F) NPphe-Rh. MH: morin hydrate; phe: phenylalanine; Rh: rhodamine B.
Figure 3
Figure 3
Mean in vitro release profiles (±SD) of MH from formulations NP-MH and NPphe-MH. MH: Morin hydrate; phe: Phenylalanine.
Figure 4
Figure 4
Mean amounts (±SD) of Rh-B in different organs at times 1 h and 2 h. * Statistically significant differences (p-value < 0.05).
Figure 5
Figure 5
Images of brain samples corresponding to: (A) non-treated (control) animals at 1 h; (B) non-treated (control) control animals at 2 h; (C) formulation NP-Rh at 1 h; (D) formulation NP-Rh at 2 h; (E) formulation NPphe-Rh at 1 h; (F) formulation NPphe-Rh at 2 h.
Figure 6
Figure 6
(A) Mean fluorescence intensity (±SD) of Rh-B in brain samples at times 1 h and 2 h measured by ImageJ software. (B) Mean amounts (±SD) of Rh-B in brain samples at times 1 h and 2 h determined by fluorescence spectrophotometry. Control corresponds to non-treated animals. * Statistically significant differences (p-value < 0.05).
See this image and copyright information in PMC

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