{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:03:52Z","timestamp":1777010632294,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The extract of Cardiospermum halicacabum L. (C. halicacabum) obtained from flower, leaf and vine was loaded into modified phospholipid vesicles aiming at obtaining sprayable, biocompatible and effective nasal spray formulations for the treatment of nasopharyngeal diseases. Penetration enhancer-containing vesicles (PEVs) and hyalurosomes were formulated, and stabilized by adding a commercial gelatin from fish (20 mg\/mL) or chondroitin sulfate from catshark cartilages (Scyliorhinus canicula, 20 mg\/mL). Cryo-TEM images confirmed the formation of spherical vesicles, while photon correlation spectroscopy analysis disclosed the formation of small and negatively-charged vesicles. PEVs were the smaller vesicles (~100 nm) along with gelatin-hyalurosomes (~120 nm), while chondroitin-PEVs and chondroitin-hyalurosomes were larger (~160 nm). Dispersions prepared with chondroitin sulfate were more homogeneous, as the polydispersity index was ~0.15. The in vitro analysis of the droplet size distribution, average velocity module and spray cone angle suggested a good spray-ability and deposition of formulations in the nasal cavity, as the mean diameter of the droplets was in the range recommended by the Food and Drug Administration for nasal targets. The spray plume analysis confirmed the ability of PEVs, gelatin-PEVs, hyalurosomes and gelatin-hyalurosomes to be atomized in fine droplets homogenously distributed in a full cone plume, with an angle ranging from 25 to 30\u00b0. Moreover, vesicles were highly biocompatible and capable of protecting the epithelial cells against oxidative damage, thus preventing the inflammatory state.<\/jats:p>","DOI":"10.3390\/molecules26216670","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T09:11:32Z","timestamp":1636017092000},"page":"6670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design of a Nasal Spray Based on Cardiospermum halicacabum Extract Loaded in Phospholipid Vesicles Enriched with Gelatin or Chondroitin Sulfate"],"prefix":"10.3390","volume":"26","author":[{"given":"Eleonora","family":"Casula","sequence":"first","affiliation":[{"name":"Department of Scienze della Vita e dell\u2019Ambiente, Sezione di Scienze del Farmaco, University of Cagliari, Via Ospedale n. 72, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-2344","authenticated-orcid":false,"given":"Maria","family":"Manconi","sequence":"additional","affiliation":[{"name":"Department of Scienze della Vita e dell\u2019Ambiente, Sezione di Scienze del Farmaco, University of Cagliari, Via Ospedale n. 72, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1122-4726","authenticated-orcid":false,"given":"Jos\u00e9","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Group of Recycling and Valorization of Waste Materials (REVAL), Marine Research Institute (IIM-CSIC), C\/Eduardo Cabello, 6, 36208 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Lopez-Mendez","sequence":"additional","affiliation":[{"name":"NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 01006 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-2267","authenticated-orcid":false,"given":"Jos\u00e9","family":"Pedraz","sequence":"additional","affiliation":[{"name":"NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV\/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain"},{"name":"Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 01006 Vitoria-Gasteiz, Spain"},{"name":"Bioaraba, NanoBioCel Research Group, Calle Jos\u00e9 Achotegui s\/n., 01009 Vitoria-Gasteiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esteban","family":"Calvo","sequence":"additional","affiliation":[{"name":"Laboratory for Research in Fluid Dynamics and Combustion Technology (LIFTEC), Consejo Superior de Investigaciones Cientificas (CSIC)\u2013Universidad de Zaragoza, Mar\u00eda de Luna, 10, 50018 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4141-6072","authenticated-orcid":false,"given":"Antonio","family":"Lozano","sequence":"additional","affiliation":[{"name":"Laboratory for Research in Fluid Dynamics and Combustion Technology (LIFTEC), Consejo Superior de Investigaciones Cientificas (CSIC)\u2013Universidad de Zaragoza, Mar\u00eda de Luna, 10, 50018 Zaragoza, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Zaru","sequence":"additional","affiliation":[{"name":"Icnoderm S.r.l., Sardegna Ricerche Ed. 5, Pula, 09010 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia","family":"Ascenso","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, University of Lisbona, Av. Gama Pinto, 1649-003 Lisbona, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-257X","authenticated-orcid":false,"given":"Maria","family":"Manca","sequence":"additional","affiliation":[{"name":"Department of Scienze della Vita e dell\u2019Ambiente, Sezione di Scienze del Farmaco, University of Cagliari, Via Ospedale n. 72, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"ref_1","first-page":"1005","article-title":"Pharmacological Properties of Cardiospermum halicacabum-A Review","volume":"5","author":"Murti","year":"2010","journal-title":"Sect. Title Pharmacol."},{"key":"ref_2","first-page":"371","article-title":"Review of Ethnobotanical, Phytochemical and Pharmacological Profile of Cardiospermum halicacabum Linn","volume":"6","author":"Sharma","year":"2018","journal-title":"Int. J. Pharm. Drug Anal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111718","DOI":"10.1016\/j.jphotobiol.2019.111718","article-title":"Zinc Oxide Nanoparticles Synthesized from Cardiospermum halicacabum and Its Anticancer Activity in Human Melanoma Cells (A375) through the Modulation of Apoptosis Pathway","volume":"202","author":"Duan","year":"2020","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.5897\/AJPP2013.3719","article-title":"Review of Beneficial and Remedial Aspects of Cardiospermum halicacabum L.","volume":"7","author":"Raza","year":"2013","journal-title":"Afr. J. Pharm. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3897\/neobiota.19.5279","article-title":"The Ecology, Biogeography, History and Future of Two Globally Important Weeds: Cardiospermum halicacabum Linn. and C. grandiflorum Sw","volume":"19","author":"Gildenhuys","year":"2013","journal-title":"NeoBiota"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/S2221-1691(12)60105-1","article-title":"Repellent Properties of Cardiospermum halicacabum Linn. (Family: Sapindaceae) Plant Leaf Extracts against Three Important Vector Mosquitoes","volume":"2","author":"Govindarajan","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.2147\/DDDT.S155610","article-title":"Antifungal Activity of Cardiospermum halicacabum L. (Sapindaceae) against Trichophyton rubrum Occurs through Molecular Interaction with Fungal Hsp90","volume":"12","author":"Gaziano","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jep.2005.02.017","article-title":"The in Vitro and in Vivo Antimalarial Activity of Cardiospermum halicacabum L. and Momordica foetida Schumch. Et Thonn","volume":"99","author":"Waako","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.5958\/0974-360X.2019.00267.1","article-title":"Evaluation of Diuretic Activity on Leaves Extract of Cardiospermum halicacabum Linn","volume":"12","author":"Velmurugan","year":"2019","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_10","first-page":"1000120","article-title":"Traditional Herbal Medicines for the Treatment of Snake Bite and Scorpion Sting by the Tribes of South Surguja, Chhattisgarh, India","volume":"2","year":"2013","journal-title":"Med. Aromat. Plants"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3109\/14756366.2013.840614","article-title":"Chemical Profiling and in Vitro Biological Effects of Cardiospermum halicacabum L. (Sapindaceae) Aerial Parts and Seeds for Applications in Neurodegenerative Disorders","volume":"29","author":"Menichini","year":"2014","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s12088-012-0333-4","article-title":"Chemical Constituents and Antimicrobial Activity of Indian Green Leafy Vegetable Cardiospermum halicacabum","volume":"53","author":"Jeyadevi","year":"2013","journal-title":"Indian J. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Francenia Santos-S\u00e1nchez, N., Salas-Coronado, R., Villanueva-Ca\u00f1ongo, C., and Hern\u00e1ndez-Carlos, B. (2019). Antioxidant Compounds and Their Antioxidant Mechanism. Antioxidants, IntechOpen.","DOI":"10.5772\/intechopen.85270"},{"key":"ref_14","first-page":"302","article-title":"Preliminary Phytochemical Screening and Antibacterial Activity of Medicinal Plant Cardiospermum halicacabum L.","volume":"4","author":"Annadurai","year":"2013","journal-title":"Adv. Appl Sci Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s13346-012-0108-9","article-title":"Nasal Drug Delivery Devices: Characteristics and Performance in a Clinical Perspective-a Review","volume":"3","author":"PG","year":"2013","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"196","DOI":"10.5414\/ALP33196","article-title":"Treating Seasonal Allergic Rhinoconjunctivitis with a Liposomal Nasal Spray","volume":"33","author":"Weston","year":"2010","journal-title":"Allergologie"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00405-011-1696-6","article-title":"Liposomes: A New Non-Pharmacological Therapy Concept for Seasonal-Allergic-Rhinoconjunctivitis","volume":"269","author":"Avgitidou","year":"2012","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biomaterials.2015.08.034","article-title":"Development of Curcumin Loaded Sodium Hyaluronate Immobilized Vesicles (Hyalurosomes) and Their Potential on Skin Inflammation and Wound Restoring","volume":"71","author":"Manca","year":"2015","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jep.2010.11.005","article-title":"Antioxidant and Anti-Inflammatory Properties of Cardiospermum halicacabum and Its Reference Compounds Ex Vivo and in Vivo","volume":"133","author":"Huang","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41598-017-18561-x","article-title":"Enhanced Nasal Drug Delivery Efficiency by Increasing Mechanical Loading Using Hypergravity","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jconrel.2012.01.024","article-title":"Nasal Drug Delivery\u2014Recent Developments and Future Prospects","volume":"161","author":"Illum","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ghadiri, M., Young, P.M., and Traini, D. (2019). Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030113"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.compbiomed.2016.08.002","article-title":"Effects of Nasal Drug Delivery Device and Its Orientation on Sprayed Particle Deposition in a Realistic Human Nasal Cavity","volume":"77","author":"Tong","year":"2016","journal-title":"Comput. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.compbiomed.2008.03.008","article-title":"Optimising Nasal Spray Parameters for Efficient Drug Delivery Using Computational Fluid Dynamics","volume":"38","author":"Inthavong","year":"2008","journal-title":"Comput. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0169-409X(97)00067-7","article-title":"Nasal Delivery Systems and Their Effect on Deposition and Absorption","volume":"29","author":"Kublik","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.drudis.2015.10.016","article-title":"Smart Materials: In Situ Gel-Forming Systems for Nasal Delivery","volume":"21","author":"Karavasili","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_27","first-page":"202","article-title":"Water Vapor Permeability of Mammalian and Fish Gelatin Films","volume":"71","author":"Olsen","year":"2006","journal-title":"J. Food Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1517\/17425247.2015.1037272","article-title":"Drug Delivery from Gelatin-Based Systems","volume":"12","author":"Foox","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0049-3848(00)00365-0","article-title":"Importance of GlcUA\u03b21-3Ga1NAc(4S,6S) in Chondroitin Sulfate E for t-PA- and u-PA-Mediated Glu-Plasminogen Activation","volume":"100","author":"Sakai","year":"2000","journal-title":"Thromb. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.carbpol.2018.05.019","article-title":"Chondroitin Sulfate\/Dermatan Sulfate from Corb (Sciaena Umbra) Skin: Purification, Structural Analysis and Anticoagulant Effect","volume":"196","author":"Bougatef","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.joca.2010.01.016","article-title":"Antioxidant, Antiinflammatory and Neuroprotective Actions of Chondroitin Sulfate and Proteoglycans","volume":"18","author":"Egea","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.carbpol.2016.09.050","article-title":"By-Products of Scyliorhinus canicula, Prionace Glauca and Raja Clavata: A Valuable Source of Predominantly 6S Sulfated Chondroitin Sulfate","volume":"157","author":"Blanco","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.3390\/md13063287","article-title":"Production of Chondroitin Sulphate from Head, Skeleton and Fins of Scyliorhinus canicula by-Products by Combination of Enzymatic, Chemical Precipitation and Ultrafiltration Methodologies","volume":"13","author":"Blanco","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1093\/glycob\/cwp123","article-title":"Structural Analysis of Chondroitin Sulfate from Scyliorhinus canicula: A Useful Source of This Polysaccharide","volume":"19","author":"Gargiulo","year":"2009","journal-title":"Glycobiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.colsurfb.2014.03.010","article-title":"Molecular Arrangements and Interconnected Bilayer Formation Induced by Alcohol or Polyalcohol in Phospholipid Vesicles","volume":"117","author":"Manca","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ijpharm.2014.10.031","article-title":"Development of Novel Diolein-Niosomes for Cutaneous Delivery of Tretinoin: Influence of Formulation and in Vitro Assessment","volume":"477","author":"Manca","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1089\/jam.2007.0638","article-title":"The Influence of Spray Properties on Intranasal Deposition","volume":"20","author":"Foo","year":"2007","journal-title":"J. Aerosol Med. Depos. Clear. Eff. Lung"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.resp.2008.07.023","article-title":"Digital Particle Image Velocimetry Studies of Nasal Airflow","volume":"163","author":"Chung","year":"2008","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_39","unstructured":"FDA (2021, July 28). Guidance for Industry Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products, Available online: https:\/\/www.fda.gov\/media\/70857\/download,."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3390\/pharmaceutics6020195","article-title":"Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S","volume":"6","author":"Trows","year":"2014","journal-title":"Pharmaceutics"},{"key":"ref_41","unstructured":"USP, FDA, and CDER (2013, June 04). Guidance for Industry Guidance for Industry Bioavailability and Bioequivalence Studies for Nasal Aerosols and Nasal Sprays for Local Action (Draft Guidance), Available online: Http:\/\/Www.Fda.Gov\/Downloads\/Drugs\/GuidanceComplianceRegulatoryInformati."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1208\/s12249-013-0062-y","article-title":"Advances in Metered Dose Inhaler Technology: Hardware Development","volume":"15","author":"Stein","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Casula, E., Manca, M.L., Perra, M., Pedraz, J.L., Lopez-Mendez, T.B., Lozano, A., Calvo, E., Zaru, M., and Manconi, M. (2021). Nasal Spray Formulations Based on Combined Hyalurosomes and Glycerosomes Loading Zingiber Officinalis Extract as Green and Natural Strategy for the Treatment of Rhinitis and Rhinosinusitis. Antioxidants, 10.","DOI":"10.3390\/antiox10071109"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0894-1777(95)00086-0","article-title":"An Investigation of the near Wake of a Circular Cylinder Using a Video-Based Digital Cross-Correlation Particle Image Velocimetry Technique","volume":"12","author":"Soria","year":"1996","journal-title":"Exp. Therm. Fluid Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1208\/s12249-016-0564-5","article-title":"High-Speed Laser Image Analysis of Plume Angles for Pressurised Metered Dose Inhalers: The Effect of Nozzle Geometry","volume":"18","author":"Chen","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_46","unstructured":"Canada, H. (2021, July 28). Pharmaceutical Quality of Inhalation and Nasal Products. Available online: https:\/\/www.ema.europa.eu\/en\/pharmaceutical-quality-inhalation-nasal-products."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ijpharm.2019.02.026","article-title":"How to Characterize a Nasal Product. The State of the Art of in Vitro and Ex Vivo Specific Methods","volume":"561","author":"Salade","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1556-276X-8-102","article-title":"Liposome: Classification, Preparation, and Applications","volume":"8","author":"Akbarzadeh","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1021\/acs.molpharmaceut.7b00702","article-title":"Personalized Medicine in Nasal Delivery: The Use of Patient-Specific Administration Parameters to Improve Nasal Drug Targeting Using 3D-Printed Nasal Replica Casts","volume":"15","author":"Warnken","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.jconrel.2013.09.019","article-title":"Gelatin-Based Nanoparticles as Drug and Gene Delivery Systems: Reviewing Three Decades of Research","volume":"172","author":"Elzoghby","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"146","DOI":"10.29252\/IJMR-050404","article-title":"Cardiospermum halicacabum Linn.: Food and Drug","volume":"5","author":"Ferrara","year":"2018","journal-title":"Int. J. Med. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Goyanes, S.N., and D\u2019Accorso, N.B. (2017). Industrial Applications of Renewable Biomass Products: Past, Present and Future, Springer.","DOI":"10.1007\/978-3-319-61288-1"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"116441","DOI":"10.1016\/j.carbpol.2020.116441","article-title":"do R. Hyaluronic Acid and Chondroitin Sulfate from Marine and Terrestrial Sources: Extraction and Purification Methods","volume":"243","author":"Abdallah","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_54","unstructured":"Kommareddy, S., Shenoy, D.B., and Amiji, M.M. (2007). Gelatin Nanoparticles and Their Biofunctionalization. Nanotechnologies for the Life Sciences, Wiley-VCH."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"110407","DOI":"10.1016\/j.colsurfb.2019.110407","article-title":"Strategies for Surface Modification of Gelatin-Based Nanoparticles","volume":"183","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1021\/acs.bioconjchem.9b00221","article-title":"Chondroitin Sulfate-Based PH-Sensitive Polymer-Modified Liposomes for Intracellular Antigen Delivery and Induction of Cancer Immunity","volume":"30","author":"Okubo","year":"2019","journal-title":"Bioconjugate Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Natsheh, H., and Touitou, E. (2020). Phospholipid Vesicles for Dermal\/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties. Molecules, 25.","DOI":"10.3390\/molecules25132959"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1080\/02786820600924978","article-title":"A Numerical Study of Spray Particle Deposition in a Human Nasal Cavity","volume":"40","author":"Inthavong","year":"2006","journal-title":"Aerosol Sci. Technol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/02786820600660903","article-title":"Airflow and Deposition of Nano-Particles in a Human Nasal Cavity","volume":"40","author":"Zamankhan","year":"2006","journal-title":"Aerosol Sci. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Calmet, H., Inthavong, K., Eguzkitza, B., Lehmkuhl, O., Houzeaux, G., and V\u00e1zquez, M. (2019). Nasal Sprayed Particle Deposition in a Human Nasal Cavity under Different Inhalation Conditions. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221330"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1007\/s11095-005-7391-9","article-title":"The Effect of Formulation Variables and Breathing Patterns on the Site of Nasal Deposition in an Anatomically Correct Model","volume":"22","author":"Guo","year":"2005","journal-title":"Pharm. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1089\/08942680152484199","article-title":"Characterization of Nasal Spray Pumps and Deposition Pattern in a Replica of the Human Nasal Airway","volume":"14","author":"Cheng","year":"2001","journal-title":"J. Aerosol Med. Depos. Clear. Eff. Lung"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1007\/s11095-011-0417-6","article-title":"Effect of Formulation- and Administration-Related Variables on Deposition Pattern of Nasal Spray Pumps Evaluated Using a Nasal Cast","volume":"28","author":"Kundoor","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1080\/02786826.2014.931566","article-title":"A Comparison of the Deposition Patterns of Different Nasal Spray Formulations Using a Nasal Cast","volume":"48","author":"Pu","year":"2014","journal-title":"Aerosol Sci. Technol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0168-3659(02)00363-2","article-title":"Nasal Drug Delivery\u2014Possibilities, Problems and Solutions","volume":"87","author":"Illum","year":"2003","journal-title":"J. Control. Release"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.ijbiomac.2020.05.229","article-title":"Development of Chitosan, Gelatin and Liposome Film and Analysis of Its Biocompatibility in Vitro","volume":"160","author":"Vedovatto","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7432797","DOI":"10.1155\/2016\/7432797","article-title":"Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?","volume":"2016","author":"Hussain","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ejpb.2017.02.004","article-title":"Bifunctional Viscous Nanovesicles Co-Loaded with Resveratrol and Gallic Acid for Skin Protection against Microbial and Oxidative Injuries","volume":"114","author":"Vitonyte","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1021\/tx9600964","article-title":"A Quantum Chemical Explanation of the Antioxidant Activity of Flavonoids","volume":"9","author":"Tromp","year":"1996","journal-title":"Chem. Res. Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.foodchem.2011.09.020","article-title":"Characterisation of the Antioxidant Activity of Flavonoids","volume":"131","author":"Masuoka","year":"2012","journal-title":"Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:25:42Z","timestamp":1760167542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":70,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26216670"],"URL":"https:\/\/doi.org\/10.3390\/molecules26216670","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]}}}