Intranasal in situ gelling liquid crystal for delivery of resveratrol ameliorates memory and neuroinflammation in Alzheimer's disease

• Published in: Nanomedicine Vol. 51; p. 102689
• Main Authors: Fonseca-Santos, Bruno, Cazarin, Camila André, da Silva, Patrícia Bento, dos Santos, Kaio Pini, da Rocha, Márcia Cristina Oliveira, Báo, Sônia Nair, De-Souza, Márcia Maria, Chorilli, Marlus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2023
• Subjects: Administration, Intranasal; Alzheimer Disease - drug therapy; Animals; Brain; Colloids; Liquid Crystals - chemistry; Microemulsion; Neuroinflammatory Diseases; Neurological disease; Polyoxyethylene oleyl ether; Resveratrol - pharmacology; Resveratrol - therapeutic use; Scattering, Small Angle; X-Ray Diffraction; Brain; Neurological disease; Microemulsion; Polyoxyethylene oleyl ether; Colloids
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2023.102689

Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin. Novel surfactant-based systems were successfully developed for loading trans-resveratrol to delivery to the brain. Systems with desired rheological, mechanical and mucoadhesive proprieties were achieved. Pharmacodynamic assays were performed in the induced-AD model and the systems were able to reverse the loss of memory and neuroinflammation followed by intranasal administration. [Display omitted] •Mixture of oleic acid, OLETH-20 and water was able to form self-orgnized systems;•Selected systems displayed as microemulsion and undergone to the lyotropic liquid crystals;•Rheological, mechanical and mucoadeshive studies showed in situ nasal suitable purposes;•Using in-vivo AD model, it was evidenced that treatment ameloriates memory and denotes decrease of neuroinflammation;