In vivo biodistribution of venlafaxine-PLGA nanoparticles for brain delivery: plain vs. functionalized nanoparticles. (2nd December 2019)

• Record Type: Journal Article
• Authors: Cayero-Otero, M.D.; Gomes, Maria João; Martins, Cláudia; Álvarez-Fuentes, J.; Fernández-Arévalo, M.; Sarmento, B.; Martín-Banderas, L.
• Is Part Of: Expert opinion on drug delivery. Volume 16:Number 12(2019)
• Page Start: 1413
• Page End: 1427
• Publication Date: 2019-12-02
• Subjects: Depression -- PLGA nanoparticles -- venlafaxine -- blood–brain barrier -- transferrin receptor -- nose-to-brain; Drug delivery devices -- Periodicals; Drug delivery systems -- Periodicals; 615.605
• DOI: 10.1080/17425247.2019.1690452
• Languages: English
• ISSNs: 1742-5247

Abstract

ABSTRACT: Background : 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.