RT journal article T1 Venlafaxine-PLGA nanoparticles provide a fast onset of action in an animal model of depression via nose-to-brain A1 Cayero-Otero, M. Dolores A1 Perez-Caballero, Laura A1 Suárez-Pereira, Irene A1 Hidalgo Figueroa, María A1 Delgado Sequera, Alejandra Cristina A1 Montesinos, Juan Manuel A1 Berrocoso Domínguez, Esther María A1 Martín Banderas, Lucía A2 Psicología K1 Venlafaxine K1 Nose-to-brain K1 PLGA nanoparticles K1 Depression AB BackgroundCurrent treatment of depression is hindered by the delayed onset of the action of antidepressant drugs, often resulting in treatment failure. Therefore, new therapeutic solutions are imperative.MethodologyVenlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were produced by a double emulsion-solvent evaporation method. Cellular safety assessment and internalization assays were carried out in vitro in human olfactory neuroepithelium cells. The antidepressant effect of intranasal (nose-to-brain) nanoparticle administration was assessed in animals submitted to an animal model of depression by behavioral tests, including open-field, sucrose preference test and tail suspension test.ResultsThe drug entrapment efficiency (55–65 %), particle size (190–210 nm), polydispersity index (<0.2), and zeta potential (−20 mV) of Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were determined to be adequate. Nanoparticles did not show cytotoxic effects. Cell viability was more than 90 % for all formulations and concentrations assayed. The results of the quantitative and qualitative cell uptake assays were consistent, showing an evident internalization of the nanoparticles into the cells. Furthermore, venlafaxine-loaded nanoparticles administered for just 7 days were able to reverse the phenotype induced by a depressive-like model, showing a significant antidepressant-like effect compared to those treated with free venlafaxine.ConclusionsThese findings indicated that intranasal venlafaxine-loaded poly(lactic-coglycolic acid) nanoparticles could become a viable technique for improving venlafaxine brain uptake via nose-to-brain. It could also be a promising nanoplatform for enhancing the treatment of depression. PB Elsevier SN 0378-5173 YR 2025 FD 2025 LK http://hdl.handle.net/10498/36769 UL http://hdl.handle.net/10498/36769 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 10-may-2026