Marco Zaru, Esteban Calvo, Tania Belen Lopez-Mendez, Antonio Lozano, Sara Fais, Maria Manconi, Maria Letizia Manca, Germano Orrù, José Luis Pedraz, Eleonora Casula, Ines Castangia, Ministero dell'Istruzione, dell'Università e della Ricerca, European Commission, Casula, Eleonora, Manconi, Maria, López-Méndez, Tania Belén, Pedraz Muñoz, José Luis, Calvo, Esteban, Lozano Fantoba, Antonio, Castangia, Ines, Orrù, Germano, Fais, Sara, and Manca, Maria Letizia
5 figures, 4 tables., Natural nasal spray formulations were prepared by using Zingiber officinalis (Z. officinalis) extract and citral synergically loaded into specifically designed phospholipid vesicles. Phospholipid vesicles were selected according to their stabilizing effect on the nasal mucosal barrier, and their effectiveness was further potentiated by the co-loading of Z. officinalis extract as antioxidant and anti-inflammatory agent, and citral as antibacterial molecule. Cryo-TEM images confirmed the formation of morphologically homogeneous and small vesicles, sized around 100 nm, negatively charged (−44 mV) and highly biocompatible (viability ≥100%) as detected by using epithelial cells. The analysis of size distribution of sprayed droplets, average velocity module and spray cone angle suggested a good aptitude of the vesicles to be nebulized and their effective deposition in the nasal cavity. Moreover, vesicles were effectively capable of inhibiting some nasal pathogenic bacteria (i.e. Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli) and to protect the epithelial cells against oxidative damage. The formulations are natural and safe, and all of them have shown promising technological and biological properties suggesting their possible application in the nasal cavity for the treatment of congestions and non-allergic rhinitis., The authors thank PON-RI 2014–2020 Research and Innovation Program, grant number DOT1304004, for the support. The authors thank for technical and human support provided by TEM measurements carried out in the SGIker Polymer Characterization (UPV/EHU/ ERDF, EU); the NanoBioCel Group of the University of the Basque Country (UPV/EHU), in Vitoria-Gasteiz (Spain); the Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) of Zaragoza (Spain); the Molecular Biology Service Lab of the University of Cagliari.