{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:07:12Z","timestamp":1789826832495,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMR-1809541"],"award-info":[{"award-number":["DMR-1809541"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic patients are especially susceptible to chronic wounds of the skin, which can lead to serious complications. Sodium citrate is one potential therapeutic molecule for the topical treatment of diabetic ulcers, but its viability requires the assistance of a biomaterial matrix. In this study, nanofibers and thin films fabricated from natural corn zein protein are explored as a drug delivery vehicle for the topical drug delivery of sodium citrate. Corn zein is cheap and abundant in nature, and easily extracted with high purity, while nanofibers are frequently cited as ideal drug carriers due to their high surface area and high porosity. To further reduce costs, the 1-D nanofibers in this study were fabricated through an air jet-spinning method rather than the conventional electrospinning method. Thin films were also created as a comparative 2-D material. Corn zein composite nanofibers and thin films with different concentration of sodium citrate (1\u201330%) were analyzed through FTIR, DSC, TGA, and SEM. Results reveal that nanofibers are a much more effective vehicle than films, with the ability to interact with sodium citrate. Thermal analysis results show a stable material with low degradation, while FTIR reveals strong control over the protein secondary structures and hold of citrate. These tunable properties and morphologies allow the fibers to provide a sustained release of citrate and then revert to their structure prior to citrate loading. A statistical analysis via t-test confirmed a significant difference between fiber and film drug release. A biocompatibility study also confirms that cells are much more tolerant of the porous nanofiber structure than the nonporous protein films, and lower percentages of sodium citrate (1\u20135%) were outperformed to higher percentages (15\u201330%). This study demonstrated that protein-based nanofiber materials have high potential as vehicles for the delivery of topical diabetic drugs.<\/jats:p>","DOI":"10.3390\/ijms21165780","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T09:14:49Z","timestamp":1597223689000},"page":"5780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Air-Jet Spun Corn Zein Nanofibers and Thin Films with Topical Drug for Medical Applications"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1426-8150","authenticated-orcid":false,"given":"Christopher R.","family":"Gough","sequence":"first","affiliation":[{"name":"Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA"},{"name":"Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA"},{"name":"Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Bessette","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA"},{"name":"Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA"},{"name":"Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2579-2820","authenticated-orcid":false,"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Rowan University, Glassboro, NJ 08028, USA"},{"name":"Department of Biomedical Engineering, Rowan University, Glassboro, NJ 08028, USA"},{"name":"Department of Molecular and Cellular Biosciences, Rowan University, Glassboro, NJ 08028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2020). National Diabetes Statistics Report."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e178","DOI":"10.1016\/j.jcjo.2016.07.004","article-title":"Treatment of grade IV diffuse lamellar keratitis with oral doxycycline and topical 10% sodium citrate","volume":"51","author":"Jarade","year":"2016","journal-title":"Can. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1002\/adfm.201303253","article-title":"Dendron-Based Micelles for Topical Delivery of Endoxifen: A Potential Chemo-Preventive Medicine for Breast Cancer","volume":"24","author":"Yang","year":"2014","journal-title":"Adv. Funct. Mater."},{"key":"ref_4","first-page":"486","article-title":"Sodium citrate reduces the incidence of corneal ulcerations and perforations in extreme alkali-burned eyes--acetylcysteine and ascorbate have no favorable effect","volume":"21","author":"Pfister","year":"1981","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9108","DOI":"10.1167\/iovs.11-7255","article-title":"Doxycycline Enhances the Inhibitory Effects of Bevacizumab on Corneal Neovascularization and Prevents Its Side Effects","volume":"52","author":"Su","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","first-page":"1257","article-title":"The effect of sodium citrate on the stimulation of polymorphonuclear leukocytes","volume":"26","author":"Parker","year":"1985","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Takashina, Y., Manabe, A., Hasegawa, H., Matsunaga, T., Endo, S., and Ikari, A. (2018). Sodium Citrate Increases Expression and Flux of Mg 2+ Transport Carriers Mediated by Activation of MEK\/ERK\/c-Fos Pathway in Renal Tubular Epithelial Cells. Nutrients, 10.","DOI":"10.3390\/nu10101345"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.carbpol.2016.09.013","article-title":"Hyaluronan polymeric micelles for topical drug delivery","volume":"156","author":"Smejkalova","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3109\/10717544.2014.943336","article-title":"Liposomes in topical ophthalmic drug delivery: An update","volume":"23","author":"Agarwal","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s004230050010","article-title":"Acceleration of wound healing by topical drug delivery via liposomes","volume":"385","author":"Roesken","year":"2000","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S1773-2247(09)50080-9","article-title":"Applications of nanoparticles in topical drug delivery and in cosmetics","volume":"19","author":"Wu","year":"2009","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ijpharm.2010.08.012","article-title":"The role of vehicle-nanoparticle interactions in topical drug delivery","volume":"400","author":"Moddaresi","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Joachim, H., and Wendorff, S.A. (2012). Andreas Greiner, Seema Agarwal. Electrospinning: Materials, Processing, and Applications, Wiley-VCH.","DOI":"10.1002\/9783527647705"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ajps.2016.05.004","article-title":"Thin films as an emerging platform for drug delivery","volume":"11","author":"Karki","year":"2016","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jconrel.2014.04.018","article-title":"Electrospinning of polymeric nanofibers for drug delivery applications","volume":"185","author":"Hu","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/ep.10463","article-title":"Biodegradable protein-based films from plant resources: A review","volume":"29","author":"Zhang","year":"2010","journal-title":"Environ. Prog. Sustain. Energy"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bealer, E.J., Onissema-Karimu, S., Rivera-Galletti, A., Francis, M., Wilkowski, J., Salas-de la Cruz, D., and Hu, X. (2020). Protein-Polysaccharide Composite Materials: Fabrication and Applications. Polymers, 12.","DOI":"10.3390\/polym12020464"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bealer, E.J., Kavetsky, K., Dutko, S., Lofland, S., and Hu, X. (2019). Protein and Polysaccharide-Based Magnetic Composite Materials for Medical Applications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010186"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"DeFrates, K.G., Moore, R., Borgesi, J., Lin, G., Mulderig, T., Beachley, V., and Hu, X. (2018). Protein-based fiber materials in medicine: A Review. Nanomaterials, 8.","DOI":"10.3390\/nano8070457"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"DeFrates, K., Markiewicz, T., Gallo, P., Rack, A., Weyhmiller, A., Jarmusik, B., and Hu, X. (2018). Protein Polymer-Based Nanoparticles: Fabrication and Medical Applications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061717"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jao, D., Xue, Y., Medina, J., and Hu, X. (2017). Protein-Based Drug-Delivery Materials. Materials, 10.","DOI":"10.3390\/ma10050517"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1021\/acsbiomaterials.6b00119","article-title":"Protein-Based Bioelectronics","volume":"2","author":"Torculas","year":"2016","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Luo, Y., and Wang, Q. (2014). Zein-based micro-and nano-particles for drug and nutrient delivery: A review. J. Appl. Polym. Sci., 131.","DOI":"10.1002\/app.40696"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/app.24619","article-title":"Electrospinning and crosslinking of zein nanofiber mats","volume":"103","author":"Yao","year":"2007","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.foodhyd.2007.02.005","article-title":"Characterization of the morphology and thermal properties of Zein Prolamine nanostructures obtained by electrospinning","volume":"22","author":"Gimenez","year":"2008","journal-title":"Food Hydrocoll."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/pi.1829","article-title":"Preparation of ultrafine fibrous zein membranes via electrospinning","volume":"54","author":"Miyoshi","year":"2005","journal-title":"Polym. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1002\/mabi.200500140","article-title":"Effects of Processing on the Structure of Zein\/Oleic Acid Films Investigated by X-Ray Diffraction","volume":"5","author":"Wang","year":"2005","journal-title":"Macromol. Biosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1016\/j.polymer.2004.03.097","article-title":"Effect of water and tri(ethylene) glycol on the rheological properties of zein","volume":"45","author":"Selling","year":"2004","journal-title":"Polymer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jconrel.2014.06.036","article-title":"Zein in controlled drug delivery and tissue engineering","volume":"189","author":"Paliwal","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.biomaterials.2004.02.013","article-title":"Microspheres of corn protein, zein, for an ivermectin drug delivery system","volume":"26","author":"Liu","year":"2005","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1016\/j.biomaterials.2003.10.084","article-title":"Basic study of corn protein, zein, as a biomaterial in tissue engineering, surface morphology and biocompatibility","volume":"25","author":"Dong","year":"2004","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11483-010-9174-z","article-title":"Mechanical Properties of Thermo-moulded Biofilms in Relation to Proteins\/Starch Interactions","volume":"6","author":"Zeng","year":"2011","journal-title":"Food Biophysics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.colsurfb.2013.06.042","article-title":"Cell adhesion on zein films under shear stress field","volume":"111","author":"Han","year":"2013","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7387","DOI":"10.1007\/s10853-018-2061-6","article-title":"Zein\u2013Laponite nanocomposites with improved mechanical, thermal and barrier properties","volume":"53","author":"Rouf","year":"2018","journal-title":"J. Mater. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1094\/CCHEM.1997.74.6.771","article-title":"Properties and Microstructure of Plasticized Zein Films","volume":"74","author":"Lai","year":"1997","journal-title":"Cereal Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1007\/s10853-010-4395-6","article-title":"Synthesis and properties of corn zein\/montmorillonite nanocomposite films","volume":"45","author":"Luecha","year":"2010","journal-title":"J. Mater. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1002\/jbm.b.34298","article-title":"Novel zein-based multilayer wound dressing membranes with controlled release of gentamicin","volume":"107","author":"Kimna","year":"2019","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"140716","DOI":"10.1155\/2015\/140716","article-title":"Electrospinning of Nanofibers and Their Applications for Energy Devices","volume":"2015","author":"Shi","year":"2015","journal-title":"J. Nanomater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.polymer.2014.11.019","article-title":"Theoretical and experimental investigation of physical mechanisms responsible for polymer nanofiber formation in solution blowing","volume":"56","author":"Yarin","year":"2015","journal-title":"Polymer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15403","DOI":"10.1016\/j.ceramint.2014.06.028","article-title":"Facile preparation of titanium dioxide micro\/nanofibers and tubular structures by air jet spinning","volume":"40","author":"Hamdy","year":"2014","journal-title":"Ceram. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83783","DOI":"10.1039\/C6RA16986D","article-title":"A review on non-electro nanofibre spinning techniques","volume":"6","author":"Stojanovska","year":"2016","journal-title":"RSC Adv."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1517\/17425240802567846","article-title":"Polymeric carriers: Role of Geometry in Drug Delivery","volume":"5","author":"Simone","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.matchemphys.2008.07.081","article-title":"Processing of polymer nanofibers through electrospinning as drug delivery systems","volume":"113","author":"Kenawy","year":"2009","journal-title":"Mater. Chem. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5030","DOI":"10.1016\/j.polymer.2007.06.061","article-title":"Release characteristics of four model drugs from drug-loaded electrospun cellulose acetate fiber mats","volume":"48","author":"Tungprapa","year":"2007","journal-title":"Polymer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1021\/ma0610109","article-title":"Determining Beta-Sheet Crystallinity in Fibrous Proteins by Thermal Analysis and Infrared Spectroscopy","volume":"39","author":"Hu","year":"2006","journal-title":"Macromolecules"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6361","DOI":"10.1021\/acsbiomaterials.9b00577","article-title":"Formic Acid Regenerated Mori, Tussah, Eri, Thai, and Muga Silk Materials: Mechanism of Self-Assembly","volume":"5","author":"Xue","year":"2019","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109890","DOI":"10.1016\/j.msec.2019.109890","article-title":"Silk fibroin-poly(lactic acid) biocomposites: Effect of protein-synthetic polymer interactions and miscibility on material properties and biological responses","volume":"104","author":"Wang","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1021\/bm801374q","article-title":"Plasticization of Zein: A Thermomechanical, FTIR, and Dielectric Study","volume":"10","author":"Gillgren","year":"2009","journal-title":"Biomacromolecules"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1021\/la204204j","article-title":"Nanoscale characterization of zein self-assembly","volume":"28","author":"Wang","year":"2012","journal-title":"Langmuir"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1039\/c0nr00490a","article-title":"Functionalization of manganite nanoparticles and their interaction with biologically relevant small ligands: Picosecond time-resolved FRET studies","volume":"2","author":"Giri","year":"2010","journal-title":"Nanoscale"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ejpb.2004.03.028","article-title":"Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration","volume":"58","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/S1369-7021(06)71389-X","article-title":"Electrospun nanofibers: Solving global issues","volume":"9","author":"Ramakrishna","year":"2006","journal-title":"Mater. Today"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijpharm.2017.08.081","article-title":"Electrospun tri-layered zein\/PVP-GO\/zein nanofiber mats for providing biphasic drug release profiles","volume":"531","author":"Lee","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.msec.2016.12.048","article-title":"Regenerated cellulose micro-nano fiber matrices for transdermal drug release","volume":"74","author":"Liu","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Liu, H., Gough, C.R., Deng, Q., Gu, Z., Wang, F., and Hu, X. (2020). Recent Advances in Electrospun Sustainable Composites for Biomedical, Environmental, Energy, and Packaging Applications. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114019"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/16\/5780\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:59:36Z","timestamp":1760176776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/16\/5780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,12]]},"references-count":55,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ijms21165780"],"URL":"https:\/\/doi.org\/10.3390\/ijms21165780","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,12]]}}}