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)

• Published in: Neuropharmacology Vol. 253; p. 109969
• Main Authors: Herrera, Guadalupe, Scimonelli, Teresa, Lasaga, Mercedes, Granero, Gladys, Onnainty, Renée
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2024
• Subjects: Brain delivery; Memory impairment; Polysorbate 80 coated chitosan nanoparticles; α-Melanocyte stimulating hormone analog (NDP-MSH); Memory impairment; Polysorbate 80 coated chitosan nanoparticles; Brain delivery; α-Melanocyte stimulating hormone analog (NDP-MSH)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2024.109969

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. [Display omitted] •A specific brain delivery carrier [NDP-MSH]-PS80/CS NPs was successfully developed.•The [NDP-MSH]-PS80/CS NPs effectively transported NDP-MSH to the hippocampus.•The [NDP-MSH]-PS80/CS NPs reduced contextual fear memory expression in animals fed HFD.•The [NDP-MSH]-PS80/CS NPs attenuated the cognitive damage associated with HFD diet.