{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:31:16Z","timestamp":1790958676247,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014717","name":"European Social Fund","doi-asserted-by":"publisher","award":["CENTRO-04-3559-FSE-000162"],"award-info":[{"award-number":["CENTRO-04-3559-FSE-000162"]}],"id":[{"id":"10.13039\/501100014717","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\/ERDF, ESF, European Regional Development Fund (ERDF)","award":["CENTRO-04-3559-FSE-000162"],"award-info":[{"award-number":["CENTRO-04-3559-FSE-000162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bacterial conjunctivitis is a worldwide problem that, if untreated, can lead to severe complications, such as visual impairment and blindness. Topical administration of ciprofloxacin is one of the most common treatments for this infection; however, topical therapeutic delivery to the eye is quite challenging. To tackle this, nanomedicine presents several advantages compared to conventional ophthalmic dosage forms. Herein, the flash nanoprecipitation technique was applied to produce zein and hyaluronic acid nanoparticles loaded with ciprofloxacin (ZeinCPX_HA NPs). ZeinCPX_HA NPs exhibited a hydrodynamic diameter of &lt;200 nm and polydispersity index of &lt;0.3, suitable for ocular drug delivery. In addition, the freeze-drying of the nanoparticles was achieved by using mannitol as a cryoprotectant, allowing their resuspension in water without modifying the physicochemical properties. Moreover, the biocompatibility of nanoparticles was confirmed by in vitro assays. Furthermore, a high encapsulation efficiency was achieved, and a release profile with an initial burst was followed by a prolonged release of ciprofloxacin up to 24 h. Overall, the obtained results suggest ZeinCPX_HA NPs as an alternative to the common topical dosage forms available on the market to treat conjunctivitis.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081557","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T03:21:16Z","timestamp":1658978476000},"page":"1557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Ciprofloxacin-Loaded Zein\/Hyaluronic Acid Nanoparticles for Ocular Mucosa Delivery"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-2126","authenticated-orcid":false,"given":"Telma A.","family":"Jacinto","sequence":"first","affiliation":[{"name":"CPIRN-UDI\/IPG, Centro de Potencial e Inova\u00e7\u00e3o em Recursos Naturais, Unidade de Investiga\u00e7\u00e3o para o Desenvolvimento do Interior do Instituto Polit\u00e9cnico da Guarda, Avenida Dr. Francisco de S\u00e1 Carneiro, No. 50, 6300-559 Guarda, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9699-8220","authenticated-orcid":false,"given":"Breno","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CPIRN-UDI\/IPG, Centro de Potencial e Inova\u00e7\u00e3o em Recursos Naturais, Unidade de Investiga\u00e7\u00e3o para o Desenvolvimento do Interior do Instituto Polit\u00e9cnico da Guarda, Avenida Dr. Francisco de S\u00e1 Carneiro, No. 50, 6300-559 Guarda, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-0399","authenticated-orcid":false,"given":"S\u00f3nia P.","family":"Miguel","sequence":"additional","affiliation":[{"name":"CPIRN-UDI\/IPG, Centro de Potencial e Inova\u00e7\u00e3o em Recursos Naturais, Unidade de Investiga\u00e7\u00e3o para o Desenvolvimento do Interior do Instituto Polit\u00e9cnico da Guarda, Avenida Dr. Francisco de S\u00e1 Carneiro, No. 50, 6300-559 Guarda, Portugal"},{"name":"CICS-UBI, Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-8115","authenticated-orcid":false,"given":"Maximiano P.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"CPIRN-UDI\/IPG, Centro de Potencial e Inova\u00e7\u00e3o em Recursos Naturais, Unidade de Investiga\u00e7\u00e3o para o Desenvolvimento do Interior do Instituto Polit\u00e9cnico da Guarda, Avenida Dr. Francisco de S\u00e1 Carneiro, No. 50, 6300-559 Guarda, Portugal"},{"name":"CICS-UBI, Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6832-3082","authenticated-orcid":false,"given":"Paula","family":"Coutinho","sequence":"additional","affiliation":[{"name":"CPIRN-UDI\/IPG, Centro de Potencial e Inova\u00e7\u00e3o em Recursos Naturais, Unidade de Investiga\u00e7\u00e3o para o Desenvolvimento do Interior do Instituto Polit\u00e9cnico da Guarda, Avenida Dr. Francisco de S\u00e1 Carneiro, No. 50, 6300-559 Guarda, Portugal"},{"name":"CICS-UBI, Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chaudhry, I.A. (2013). Infective Conjunctivitis\u2014Its Pathogenesis, Management and Complications. Common Eye Infections, IntechOpen.","DOI":"10.5772\/45964"},{"key":"ref_2","first-page":"372","article-title":"Conjunctivitis: A Systematic Review","volume":"15","author":"Azari","year":"2020","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.18773\/austprescr.2018.016","article-title":"Common eye infections","volume":"41","author":"Watson","year":"2018","journal-title":"Aust. Prescr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"543","DOI":"10.2165\/11589020-000000000-00000","article-title":"The Role of Topical Moxifloxacin, a New Antibacterial in Europe, in the Treatment of Bacterial Conjunctivitis","volume":"31","author":"Verboven","year":"2011","journal-title":"Clin. Drug Investig."},{"key":"ref_5","unstructured":"Pippin, M.M., and Le, J.K. (2022, June 18). Bacterial Conjunctivitis, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK546683\/."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Alharbi, W.S., and Hosny, K.M. (2020). Development and optimization of ocular in situ gels loaded with ciprofloxacin cubic liquid crystalline nanoparticles. J. Drug Deliv. Sci. Technol., 57.","DOI":"10.1016\/j.jddst.2020.101710"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1039\/C9MD00120D","article-title":"Quinolone antibiotics","volume":"10","author":"Pham","year":"2019","journal-title":"Medchemcomm"},{"key":"ref_8","first-page":"207","article-title":"The new fluoroquinolones: A critical review","volume":"10","author":"Zhanel","year":"1999","journal-title":"Can. J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jsps.2013.07.003","article-title":"Design of liposomal colloidal systems for ocular delivery of ciprofloxacin","volume":"22","author":"Taha","year":"2014","journal-title":"Saudi Pharm. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Al-Joufi, F.A., Salem-Bekhit, M.M., Taha, E.I., Ibrahim, M.A., Muharram, M.M., Alshehri, S., Ghoneim, M.M., and Shakeel, F. (2022). Enhancing Ocular Bioavailability of Ciprofloxacin Using Colloidal Lipid-Based Carrier for the Management of Post-Surgical Infection. Molecules, 27.","DOI":"10.3390\/molecules27030733"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.ijbiomac.2018.05.113","article-title":"Hyaluronic-acid-modified lipid-polymer hybrid nanoparticles as an efficient ocular delivery platform for moxifloxacin hydrochloride","volume":"116","author":"Liu","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40123-020-00257-7","article-title":"Therapies Based on Nanoparticles for Eye Drug Delivery","volume":"9","author":"Santos","year":"2020","journal-title":"Ophthalmol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s12553-019-00381-w","article-title":"Application of nanoparticles in ocular drug delivery systems","volume":"10","year":"2020","journal-title":"Health Technol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vaneev, A., Tikhomirova, V., Chesnokova, N., Popova, E., Beznos, O., Kost, O., and Klyachko, N. (2021). Nanotechnology for Topical Drug Delivery to the Anterior Segment of the Eye. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212368"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.2147\/IJN.S126199","article-title":"Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone","volume":"12","author":"Ban","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Massella, D., Celasco, E., Sala\u00fcn, F., Ferri, A., and Barresi, A.A. (2018). Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure. Polymers, 10.","DOI":"10.3390\/polym10101092"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.1021\/mp400337f","article-title":"Flash Nanoprecipitation: Particle Structure and Stability","volume":"10","author":"Pustulka","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Loureiro, J., Miguel, S.P., Seabra, I.J., Ribeiro, M.P., and Coutinho, P. (2022). Single-Step Self-Assembly of Zein\u2013Honey\u2013Chitosan Nanoparticles for Hydrophilic Drug Incorporation by Flash Nanoprecipitation. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050920"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijbiomac.2022.01.180","article-title":"Osmundea sp. macroalgal polysaccharide-based nanoparticles produced by flash nanocomplexation technique","volume":"204","author":"Miguel","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1007\/s13346-020-00738-z","article-title":"Zein nanoparticles as low-cost, safe, and effective carriers to improve the oral bioavailability of resveratrol","volume":"10","author":"Nunes","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22438","DOI":"10.3390\/ijms151222438","article-title":"Recent advances in food-packing, pharmaceutical and biomedical applications of zein and zein-based materials","volume":"15","author":"Corradini","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/10717544.2019.1704942","article-title":"Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer","volume":"27","author":"Yu","year":"2020","journal-title":"Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5933","DOI":"10.1039\/c3sm50667c","article-title":"Controlled formation of hydrophobic surfaces by self-assembly of an amphiphilic natural protein from aqueous solutions","volume":"9","author":"Dong","year":"2013","journal-title":"Soft Matter"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rodrigues, D.A., Miguel, S.P., Loureiro, J., Ribeiro, M., Roque, F., and Coutinho, P. (2021). Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122030"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gagliardi, A., Voci, S., Salvatici, M.C., Fresta, M., and Cosco, D. (2021). Brij-stabilized zein nanoparticles as potential drug carriers. Colloids Surf. B Biointerfaces, 201.","DOI":"10.1016\/j.colsurfb.2021.111647"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dubashynskaya, N., Poshina, D., Raik, S., Urtti, A., and Skorik, Y.A. (2020). Polysaccharides in Ocular Drug Delivery. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010022"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wei, D., Xu, Y., and Zhu, Q. (2021). Hyaluronic acid in ocular drug delivery. Carbohydr. Polym., 264.","DOI":"10.1016\/j.carbpol.2021.118006"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kim, D.J., Jung, M.-Y., Pak, H.-J., Park, J.-H., Kim, M., Chuck, R.S., and Park, C.Y. (2021). Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-81983-1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/bjo.86.2.181","article-title":"Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye","volume":"86","author":"Aragona","year":"2002","journal-title":"Br. J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/(SICI)1097-4644(19960616)61:4<569::AID-JCB10>3.0.CO;2-B","article-title":"HA receptors: Regulators of signalling to the cytoskeleton","volume":"61","author":"Entwistle","year":"1996","journal-title":"J. Cell. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ijbiomac.2016.05.016","article-title":"The potential application of hyaluronic acid coated chitosan nanoparticles in ocular delivery of dexamethasone","volume":"89","author":"Kalam","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Butreddy, A., Dudhipala, N., Janga, K.Y., and Gaddam, R.P. (2020). Lyophilization of Small-Molecule Injectables: An Industry Perspective on Formulation Development, Process Optimization, Scale-Up Challenges, and Drug Product Quality Attributes. AAPS PharmSciTech, 21.","DOI":"10.1208\/s12249-020-01787-w"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1080\/03639045.2018.1483392","article-title":"Excipients in parenteral formulations: Selection considerations and effective utilization with small molecules and biologics","volume":"44","author":"Rayaprolu","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1002\/jps.23259","article-title":"A simple confined impingement jets mixer for flash nanoprecipitation","volume":"101","author":"Han","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ijbiomac.2015.12.044","article-title":"Chitosan\/poly-\u03b3-glutamic acid nanoparticles improve the solubility of lutein","volume":"85","author":"Hong","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Voci, S., Gagliardi, A., Salvatici, M.C., Fresta, M., and Cosco, D. (2022). Influence of the Dispersion Medium and Cryoprotectants on the Physico-Chemical Features of Gliadin- and Zein-Based Nanoparticles. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020332"},{"key":"ref_37","unstructured":"Minist\u00e9rio da Sa\u00fade, I. (2008). Farmacopeia Portuguesa 9, Instituto Nacional da Farmacia e do Medicamento."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1208\/s12249-010-9413-0","article-title":"In Situ Gelling Gelrite\/Alginate Formulations as Vehicles for Ophthalmic Drug Delivery","volume":"11","author":"Liu","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0928-0987(99)00051-2","article-title":"Rheological studies of the gelation of deacetylated gellan gum (Gelrite\u00ae) in physiological conditions","volume":"9","author":"Paulsson","year":"1999","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jconrel.2021.06.011","article-title":"Ocular drug delivery to the anterior segment using nanocarriers: A mucoadhesive\/mucopenetrative perspective","volume":"336","author":"Dave","year":"2021","journal-title":"J. Control Release"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/02652048.2018.1462416","article-title":"Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers","volume":"35","author":"Wang","year":"2018","journal-title":"J. Microencapsul."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1039\/C8SM02418A","article-title":"Amorphous nanoparticles by self-assembly: Processing for controlled release of hydrophobic molecules","volume":"15","author":"Feng","year":"2019","journal-title":"Soft Matter"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.ijbiomac.2016.09.080","article-title":"Production and characterization of polycaprolactone-hyaluronic acid\/chitosan-zein electrospun bilayer nanofibrous membrane for tissue regeneration","volume":"93","author":"Figueira","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ye, W., Zhang, G., Liu, X., Ren, Q., Huang, F., and Yan, Y. (2022). Fabrication of polysaccharide-stabilized zein nanoparticles by flash nanoprecipitation for doxorubicin sustained release. J. Drug Deliv. Sci. Technol., 70.","DOI":"10.1016\/j.jddst.2022.103183"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijbiomac.2019.07.090","article-title":"Fabrication of stable zein nanoparticles by chondroitin sulfate deposition based on antisolvent precipitation method","volume":"139","author":"Yuan","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jacinto, T.A., Rodrigues, C.F., Moreira, A.F., Miguel, S.P., Costa, E.C., Ferreira, P., and Correia, I.J. (2020). Hyaluronic acid and vitamin E polyethylene glycol succinate functionalized gold-core silica shell nanorods for cancer targeted photothermal therapy. Colloids Surf. B Biointerfaces, 188.","DOI":"10.1016\/j.colsurfb.2020.110778"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ajps.2018.05.006","article-title":"Preparation and characterization of nanoparticles from quaternized cyclodextrin-grafted chitosan associated with hyaluronic acid for cosmetics","volume":"13","author":"Sakulwech","year":"2018","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1039\/C3PY01276J","article-title":"pH-responsive nanofibers with controlled drug release properties","volume":"5","author":"Demirci","year":"2014","journal-title":"Polym. Chem."},{"key":"ref_49","first-page":"173","article-title":"Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin","volume":"1","author":"Ramasamy","year":"2011","journal-title":"3 Biotech"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.carbpol.2006.10.014","article-title":"Controlled release of ciprofloxacin hydrochloride from chitosan\/polyethylene glycol blend films","volume":"69","author":"Wang","year":"2007","journal-title":"Carbohydr. Polym."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ijpharm.2019.03.064","article-title":"Formulation and optimization of lyophilized nanosuspension tablets to improve the physicochemical properties and provide immediate release of silymarin","volume":"563","author":"Ibrahim","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.ijbiomac.2019.10.082","article-title":"Chitosan-bacterial cellulose patch of ciprofloxacin for wound dressing: Preparation and characterization studies","volume":"147","author":"Cacicedo","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"34791","DOI":"10.1039\/C6RA01996J","article-title":"Hyaluronic acid-coated poly(d,l-lactide) (PDLLA) nanofibers prepared by electrospinning and coating","volume":"6","author":"Ahire","year":"2016","journal-title":"RSC Adv."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Dhayanandamoorthy, Y., Antoniraj, M.G., Kandregula, C.A.B., and Kandasamy, R. (2020). Aerosolized hyaluronic acid decorated, ferulic acid loaded chitosan nanoparticle: A promising asthma control strategy. Int. J. Pharm., 591.","DOI":"10.1016\/j.ijpharm.2020.119958"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejps.2018.04.009","article-title":"Gallic acid loaded PEO-core\/zein-shell nanofibers for chemopreventive action on gallbladder cancer cells","volume":"119","author":"Acevedo","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Abate, M., Scotti, L., Nele, V., Caraglia, M., Biondi, M., De Rosa, G., Leonetti, C., Campani, V., Zappavigna, S., and Porru, M. (2022). Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095138"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Liu, J., Grohganz, H., L\u00f6bmann, K., Rades, T., and Hempel, N.-J. (2021). Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030389"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1021\/acs.molpharmaceut.9b00889","article-title":"Practical Approach to Modeling the Impact of Amorphous Drug Nanoparticles on the Oral Absorption of Poorly Soluble Drugs","volume":"17","author":"Stewart","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27835","DOI":"10.1039\/D0RA04971A","article-title":"Nanocarriers for ocular drug delivery: Current status and translational opportunity","volume":"10","author":"Gorantla","year":"2020","journal-title":"RSC Adv."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Mohamed, H.B., Attia Shafie, M.A., and Mekkawy, A.I. (2022). Chitosan Nanoparticles for Meloxicam Ocular Delivery: Development, In Vitro Characterization, and In Vivo Evaluation in a Rabbit Eye Model. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14050893"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ejps.2017.03.001","article-title":"Synthetic nanocarriers for the delivery of polynucleotides to the eye","volume":"103","author":"Saraiva","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Apaolaza, P.S., Busch, M., Asin-Prieto, E., Peynshaert, K., Rathod, R., Remaut, K., D\u00fcnker, N., and G\u00f6pferich, A. (2020). Hyaluronic acid coating of gold nanoparticles for intraocular drug delivery: Evaluation of the surface properties and effect on their distribution. Exp. Eye Res., 198.","DOI":"10.1016\/j.exer.2020.108151"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4333\/KPS.2010.40.S.033","article-title":"Hyaluronic Acid in Drug Delivery Systems","volume":"40","author":"Jin","year":"2010","journal-title":"J. Pharm. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1002\/jbm.a.34976","article-title":"Hyaluronic acid-based nanocomposite hydrogels for ocular drug delivery applications","volume":"102","author":"Widjaja","year":"2014","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bongiov\u00ec, F., Di Prima, G., Palumbo, F.S., Licciardi, M., Pitarresi, G., and Giammona, G. (2017). Hyaluronic Acid-Based Micelles as Ocular Platform to Modulate the Loading, Release, and Corneal Permeation of Corticosteroids. Macromol. Biosci., 17.","DOI":"10.1002\/mabi.201700261"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ricci, F., Racaniello, G.F., Lopedota, A., Laquintana, V., Arduino, I., Lopalco, A., Cutrignelli, A., Franco, M., Sigurdsson, H.H., and Denora, N. (2022). Chitosan\/sulfobutylether-\u03b2-cyclodextrin based nanoparticles coated with thiolated hyaluronic acid for indomethacin ophthalmic delivery. Int. J. Pharm., 622.","DOI":"10.1016\/j.ijpharm.2022.121905"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.colsurfb.2016.01.014","article-title":"Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: Mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability","volume":"141","author":"Zeng","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12247-018-9335-z","article-title":"Hydrogel Containing PEG-Coated Fluconazole Nanoparticles with Enhanced Solubility and Antifungal Activity","volume":"14","author":"Abdellatif","year":"2019","journal-title":"J. Pharm. Innov."},{"key":"ref_69","unstructured":"Grumezescu, A.M. (2019). Chapter 4\u2014Multifunctional nanocrystals for cancer therapy: A potential nanocarrier. Nanomaterials for Drug Delivery and Therapy, William Andrew Publishing."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8013","DOI":"10.2147\/IJN.S189295","article-title":"Selective cytotoxicity of green synthesized silver nanoparticles against the MCF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties","volume":"13","author":"Khorrami","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_71","first-page":"373","article-title":"Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use","volume":"35","author":"Monk","year":"1988","journal-title":"Drugs"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"215","DOI":"10.4314\/ovj.v6i3.9","article-title":"Antimicrobial susceptibility and minimal inhibitory concentration of Pseudomonas aeruginosa isolated from septic ocular surface disease in different animal species","volume":"6","author":"Leigue","year":"2016","journal-title":"Open Vet. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/02713680802023104","article-title":"Formulation and evaluation of ciprofloxacin hydrochloride soluble ocular drug insert","volume":"33","author":"Mundada","year":"2008","journal-title":"Curr. Eye Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1007\/s13346-020-00736-1","article-title":"Ciprofloxacin-loaded polymeric nanoparticles incorporated electrospun fibers for drug delivery in tissue engineering applications","volume":"10","author":"Anand","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.msec.2008.09.031","article-title":"Antibacterial activity of ciprofloxacin-loaded zein microsphere films","volume":"29","author":"Fu","year":"2009","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/10717544.2019.1701140","article-title":"Preparation of PLGA-chitosan based nanocarriers for enhancing antibacterial effect of ciprofloxacin in root canal infection","volume":"27","author":"Arafa","year":"2020","journal-title":"Drug Deliv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijpharm.2019.03.051","article-title":"Alginate lyase immobilized chitosan nanoparticles of ciprofloxacin for the improved antimicrobial activity against the biofilm associated mucoid P. aeruginosa infection in cystic fibrosis","volume":"563","author":"Patel","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Gheffar, C., Le, H., Jouenne, T., Schaumann, A., Corbi\u00e8re, A., Vaudry, D., LeCerf, D., and Karakasyan, C. (2021). Antibacterial Activity of Ciprofloxacin-Loaded Poly(lactic-co-glycolic acid)-Nanoparticles Against Staphylococcus aureus. Part. Part. Syst. Charact., 38.","DOI":"10.1002\/ppsc.202000253"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Xu, J., Chen, Y., Jiang, X., Gui, Z., and Zhang, L. (2019). Development of Hydrophilic Drug Encapsulation and Controlled Release Using a Modified Nanoprecipitation Method. Processes, 7.","DOI":"10.3390\/pr7060331"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Brotons-Canto, A., Gonz\u00e1lez-Navarro, C.J., Gil, A.G., Asin-Prieto, E., Saiz, M.J., and Llabr\u00e9s, J.M. (2021). Zein Nanoparticles Improve the Oral Bioavailability of Curcumin in Wistar Rats. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030361"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ghalei, S., Asadi, H., and Ghalei, B. (2018). Zein nanoparticle-embedded electrospun PVA nanofibers as wound dressing for topical delivery of anti-inflammatory diclofenac. J. Appl. Polym. Sci., 135.","DOI":"10.1002\/app.46643"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lin, M., Fang, S., Zhao, X., Liang, X., and Wu, D. (2020). Natamycin-loaded zein nanoparticles stabilized by carboxymethyl chitosan: Evaluation of colloidal\/chemical performance and application in postharvest treatments. Food Hydrocoll., 106.","DOI":"10.1016\/j.foodhyd.2020.105871"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Reboredo, C., Gonz\u00e1lez-Navarro, C.J., Mart\u00ednez-L\u00f3pez, A.L., Mart\u00ednez-Oh\u00e1rriz, C., Sarmento, B., and Irache, J.M. (2022). Zein-Based Nanoparticles as Oral Carriers for Insulin Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010039"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Saraswathy, K., Agarwal, G., and Srivastava, A. (2020). Hyaluronic acid microneedles-laden collagen cryogel plugs for ocular drug delivery. J. Appl. Polym. Sci., 137.","DOI":"10.1002\/app.49285"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ejpb.2018.04.023","article-title":"Self-assembled amphiphilic zein-lactoferrin micelles for tumor targeted co-delivery of rapamycin and wogonin to breast cancer","volume":"128","author":"Sabra","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.ijbiomac.2018.06.061","article-title":"Properties and in vitro drug release of pH- and temperature-sensitive double cross-linked interpenetrating polymer network hydrogels based on hyaluronic acid\/poly (N-isopropylacrylamide) for transdermal delivery of luteolin","volume":"118","author":"Kim","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ijbiomac.2018.10.041","article-title":"Production and characterization of electrospun silk fibroin based asymmetric membranes for wound dressing applications","volume":"121","author":"Miguel","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Labib, B.A., and Chigbu, D.I. (2022). Therapeutic Targets in Allergic Conjunctivitis. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050547"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Fukuda, K. (2020). Corneal fibroblasts: Function and markers. Exp. Eye Res., 200.","DOI":"10.1016\/j.exer.2020.108229"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1557\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:57:12Z","timestamp":1760140632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":89,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["pharmaceutics14081557"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14081557","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]}}}