2026-06-14T00:39:35Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/193702025-02-04T12:43:00Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Nozal, Vanesa author Fernández-Gómez, Paula author García-Rubia, Alfonso author Martínez-González, Loreto author Cuevas, Eva P author Carro, Eva author Palomo, Valle author Martínez, Ana author 2024-04-24 Multitarget ligands (MTLs) have emerged as an interesting alternative for addressing complex multifactorial pathologies such as neurodegenerative diseases. However, a common challenge associated with these compounds is often their high molecular weight and low solubility, which becomes a hurdle when trying to permeate over the blood-brain barrier (BBB). In this study, we have designed two new MTLs that modulate three pharmacological targets simultaneously (tau, beta-amyloid and TAR DNA-binding protein 43). To enhance their brain penetration, we have formulated organic polymeric nanoparticles using poly(lactic-co-glycolic acid). The characterization of the formulations, evaluation of their permeability through an in vitro BBB model, and assessment of their activity on disease-representative cellular models, such as Alzheimer's disease and amyotrophic lateral sclerosis, have been conducted. The results demonstrate the potential of the new MTLs and their nanoparticle encapsulation for the treatment of neurodegenerative diseases. Biomed Pharmacother. 2024 Apr 24:175:116626. 10.1016/j.biopha.2024.116626 1950-6007 Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 38663103 http://hdl.handle.net/20.500.12105/19370 Multitarget ligand Blood-brain barrier Nanoparticles Protein kinase inhibitors Alzheimer’s disease Amyotrophic lateral sclerosis Designing multitarget ligands for neurodegenerative diseases with improved permeability trough PLGA nanoencapsulation