Cayero Otero, María DoloresGomes, Maria JoãoMartins, CláudiaÁlvarez Fuentes, JosefaFernández Arévalo, María MercedesSarmento, BrunoMartín Banderas, Lucía2024-12-202024-12-202019Cayero Otero, M.D., Gomes, M.J.,...,Martín Banderas, L. (2019). In vivo biodistribution of venlafaxine-PLGA nanoparticles for brain delivery: plain vs. functionalized nanoparticles. idUS (Depósito de Investigación de la Universidad de Sevilla). https://doi.org/10.1080/17425247.2019.1690452.1742-52471744-7593https://hdl.handle.net/11441/166029Background: Actually, no drugs provide therapeutic benefit to approximately one-third of depressed patients. Depression is predicted to become the first global disease by 2030. So, new therapeutic interventions are imperative. Research design and methods: Venlafaxine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were surface functionalized with two ligands against transferrin receptor to enhance access to brain. An in vitro blood–brain barrier model using hCMEC/D3 cell line was developed to evaluate permeability. In vivo biodistribution studies were performed using C57/bl6 mice. Particles were administered intranasal and main organs were analyzed. Results: Particles were obtained as a lyophilized powder easily to re-suspend. Internalization and permeability studies showed the following cell association sequence: TfRp-NPs>Tf-NPs>plain NPs. Permeability studies also showed that encapsulated VLF was not affected by P-gP pump efflux increasing its concentration in the basolateral side after 24 h. In vivo studies showed that 25% of plain NPs reach the brain after 30 min of one intranasal administration while less than 5% of functionalized NPs get the target. Conclusions: Plain NPs showed the highest ability to reach the brain vs. functionalized NPs after 30 min by intranasal administration. We suggest plain NPs probably travel via direct nose-to-brian route whereas functionalized NPs reach the brain by receptor-mediated endocytosis.application/pdf42 p.engAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/DepressionPLGA nanoparticlesVenlafaxineBlood–brain barrierTransferrin receptorNose-to-braininfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1080/17425247.2019.1690452