2025-07-102025-07-102025Cayero Otero, M.D., Pérez Caballero, L., Suárez Pereira, I., Hidalgo Figueroa, M., Delgado Sequera, A., Montesinos, J.M.,...,Martín Banderas, L. (2025). Venlafaxine-PLGA Nanoparticles Provide a Fast Onset of Action in an Animal Model of Depression Via Nose-to-brain. International Journal of Pharmaceutics, 678, 125692. https://doi.org/10.1016/j.ijpharm.2025.125692.0378-51731873-3476https://hdl.handle.net/11441/175227Background: Current 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. Methodology: Venlafaxine-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. Results: The 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. Conclusions: These 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.application/pdf11 p.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/VenlafaxineNose-to-brainPLGA nanoparticlesDepressioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccess10.1016/j.ijpharm.2025.125692