Polysorbate 80 coated chitosan nanoparticles for delivery of α-melanocyte stimulating hormone analog (NDP-MSH) to the brain reverse cognitive impairment related to neuroinflammation produced by a high-fat diet (HFD).

Autor: Herrera G; Instituto de Farmacología Experimental de Córdoba, IFEC-CONICET. Departamento de Farmacología Otto Orshinger, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Scimonelli T; Instituto de Farmacología Experimental de Córdoba, IFEC-CONICET. Departamento de Farmacología Otto Orshinger, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Lasaga M; Instituto de Investigaciones Biomédicas INBIOMED UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Argentina., Granero G; Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), UNC-CONICET, Departamento de Ciencias Farmacéuticas, Universidad Nacional de Córdoba, Córdoba, Argentina., Onnainty R; Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), UNC-CONICET, Departamento de Ciencias Farmacéuticas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: ronnainty@unc.edu.ar.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2024 Aug 01; Vol. 253, pp. 109969. Date of Electronic Publication: 2024 Apr 28.
DOI: 10.1016/j.neuropharm.2024.109969
Abstrakt: This study aimed to develop polysorbate 80-coated chitosan nanoparticles (PS80/CS NPs) as a delivery system for improved brain targeting of α-Melanocyte Stimulating Hormone analog (NDP-MSH). Chitosan nanoparticles loaded with NDP-MSH were surface-modified with polysorbate 80 ([NDP-MSH]-PS80/CS NP), which formed a flattened layer on their surface. Nanoparticle preparation involved ionic gelation, followed by characterization using scanning electron microscopy (SEM) for morphology, dynamic light scattering (DLS) for colloidal properties, and ATR-FTIR spectroscopy for structure. Intraperitoneal injection of FITC-PS80/CS NPs and [NDP-MSH]-PS80/CS NP in rats demonstrated their ability to cross the blood-brain barrier, reach the brain, and accumulate in CA1 neurons of the dorsal hippocampus within 2 h. Two experimental models of neuroinflammation were employed with Male Wistar rats: a short-term model involving high-fat diet (HFD) consumption for 5 days followed by an immune stimulus with LPS, and a long-term model involving HFD consumption for 8 weeks. In both models, [NDP-MSH]-PS80/CS NPs could reverse the decreased expression of contextual fear memory induced by the diets. These findings suggest that [NDP-MSH]-PS80/CS NPs offer a promising strategy to overcome the limitations of NDP-MSH regarding pharmacokinetics and enzymatic stability. By facilitating NDP-MSH delivery to the hippocampus, these nanoparticles can potentially mitigate the cognitive impairments associated with HFD consumption and neuroinflammation.
Competing Interests: Declaration of competing interest The authors declare no competing financial interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE