{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:36:02Z","timestamp":1785418562188,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Culture and Innovation of Hungary","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}],"id":[{"id":"https:\/\/ror.org\/03vhmm238","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Szeged OA Grant","award":["8758"],"award-info":[{"award-number":["8758"]}]},{"award":["8758"],"award-info":[{"award-number":["8758"]}],"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Oral protein delivery is a major challenge in the field of pharmaceutical technology due to poor stability and limited permeability through intestinal barriers. Buccal delivery is a promising alternative with less restricting physiological conditions; however, low protein permeability is still a limiting factor. Multiple nanocarriers have been proposed to improve buccal protein delivery with lipid\u2013polymer hybrid nanoparticles (LPHNs) combining the advantages of both polymeric and lipid-based systems. However, these conventional carriers rely on passive protein protection and lack adaptive release mechanisms. Objectives: This work aimed to develop and systematically optimize an ionic strength-responsive LPHN system that can minimize protein release in buccal ionic conditions while offering a triggered release in plasma after absorption. Methods: LPHNs were prepared by a two-step approach where polymeric cores of Eudragit-L100 were prepared by electrostatic complexation with Lysozyme (LYZ) followed by lipid shell formation by the ethanol injection method. Systematic optimization was performed using two-level factorial and central composite designs. Moreover, the ionic strength responsiveness and in vitro LYZ release were investigated in different ionic strength media. Results: The final optimized formulations, LPHNs and sodium deoxycholate-containing LPHNs (NaDC-LPHNs), exhibited a particle size of 257.2 \u00b1 1.5 nm and 246 \u00b1 5.7 nm, encapsulation efficiency of 69.89 \u00b1 0.22% and 68.14 \u00b1 0.16%, and high drug loading efficiency of 24.11 \u00b1 0.06% and 23.65 \u00b1 0.04%, respectively. Moreover, both formulations showed minimal protein release at low ionic strength (buccal-like) conditions while demonstrating a triggered release at higher ionic strength (plasma-like) conditions. Conclusions: The developed system may provide a promising smart strategy to improve buccal protein delivery by enhancing buccal protection and improving systemic delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060719","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:56:31Z","timestamp":1781675791000},"page":"719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Optimization of Ionic Strength-Responsive Lipid\u2013Polymer Hybrid Nanoparticles for Buccal Protein Delivery"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-1452","authenticated-orcid":false,"given":"Eslam","family":"Ramadan","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nooh","family":"Mdrmah","sequence":"additional","affiliation":[{"name":"Graduate School of Health and Drug Sciences, University of Paris-Saclay, 17, Avenue des Sciences, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2288-0948","authenticated-orcid":false,"given":"Martin","family":"De\u00e1k","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9667-6608","authenticated-orcid":false,"given":"Norbert","family":"Varga","sequence":"additional","affiliation":[{"name":"Interdisciplinary Excellence Center, Department of Physical Chemistry and Materials Science, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary"},{"name":"MTA-SZTE Lend\u00fclet \u201cMomentum\u201d Noble Metal Nanostructures Research Group, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-9524","authenticated-orcid":false,"given":"Edit","family":"Csap\u00f3","sequence":"additional","affiliation":[{"name":"Interdisciplinary Excellence Center, Department of Physical Chemistry and Materials Science, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary"},{"name":"MTA-SZTE Lend\u00fclet \u201cMomentum\u201d Noble Metal Nanostructures Research Group, University of Szeged, Rerrich B. Sqr. 1, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3392-7788","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Sov\u00e1ny","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-6831","authenticated-orcid":false,"given":"Katalin","family":"Krist\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, E\u00f6tv\u00f6s u. 6., H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/ddr.21832","article-title":"Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability","volume":"82","author":"Verma","year":"2021","journal-title":"Drug Dev. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1517\/17425247.2014.917077","article-title":"Oral peptide and protein delivery: Intestinal obstacles and commercial prospects","volume":"11","author":"Smart","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/10717544.2013.819611","article-title":"Oral delivery of therapeutic proteins and peptides: A review on recent developments","volume":"20","author":"Gupta","year":"2013","journal-title":"Drug Deliv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11095-014-1485-1","article-title":"Enhancing the buccal mucosal delivery of peptide and protein therapeutics","volume":"32","author":"Caon","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ejpb.2011.05.010","article-title":"Enhanced transbuccal salmon calcitonin (sCT) delivery: Effect of chemical enhancers and electrical assistance on in vitro sCT buccal permeation","volume":"79","author":"Oh","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bashyal, S., Seo, J.E., Keum, T., Noh, G., Lamichhane, S., and Lee, S. (2021). Development, Characterization, and Ex Vivo Assessment of Elastic Liposomes for Enhancing the Buccal Delivery of Insulin. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040565"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.ejpb.2014.06.011","article-title":"Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs","volume":"88","author":"Fan","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_8","first-page":"743","article-title":"Oral insulin delivery by means of solid lipid nanoparticles","volume":"2","author":"Sarmento","year":"2007","journal-title":"Int. J. Nanomed."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shahzadi, I., F\u00fcrst, A., Knoll, P., and Bernkop-Schn\u00fcrch, A. (2021). Nanostructured lipid carriers (NLCs) for oral peptide drug delivery: About the impact of surface decoration. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13081312"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8569","DOI":"10.1016\/j.biomaterials.2012.07.063","article-title":"Size-dependent absorption mechanism of polymeric nanoparticles for oral delivery of protein drugs","volume":"33","author":"He","year":"2012","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hassan, A.A.A., Ramadan, E., Krist\u00f3, K., Regdon, G., and Sov\u00e1ny, T. (2025). Lipid-Polymer Hybrid Nanoparticles as a Smart Drug Delivery System for Peptide\/Protein Delivery. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17060797"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jacob, S., Varkey, N.R., Boddu, S.H.S., Gorain, B., Rao, R., and Nair, A.B. (2025). Advances in Lipid-Polymer Hybrid Nanoparticles: Design Strategies, Functionalization, Oncological and Non-Oncological Clinical Prospects. Pharmaceuticals, 18.","DOI":"10.3390\/ph18121772"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hua, S. (2019). Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01328"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/smll.201201789","article-title":"In-Vitro Permeability of Neutral Polystyrene Particles via Buccal Mucosa","volume":"9","author":"Teubl","year":"2013","journal-title":"Small"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.msec.2016.11.030","article-title":"Internal stimuli-responsive nanocarriers for drug delivery: Design strategies and applications","volume":"71","author":"Liu","year":"2017","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chountoulesi, M., Naziris, N., Pippa, N., Pispas, S., and Demetzos, C. (2020). Stimuli-responsive nanocarriers for drug delivery. Nanomaterials for Clinical Applications, Elsevier.","DOI":"10.1016\/B978-0-12-816705-2.00004-7"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"AlSawaftah, N.M., Awad, N.S., Pitt, W.G., and Husseini, G.A. (2022). pH-Responsive Nanocarriers in Cancer Therapy. Polymers, 14.","DOI":"10.3390\/polym14050936"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21107","DOI":"10.1021\/acsami.6b00371","article-title":"Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances","volume":"8","author":"Karimi","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rajes, K., Walker, K.A., Hadam, S., Zabihi, F., Rancan, F., Vogt, A., and Haag, R. (2020). Redox-Responsive Nanocarrier for Controlled Release of Drugs in Inflammatory Skin Diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010037"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Li, M., Zhao, G., Su, W.K., and Shuai, Q. (2020). Enzyme-Responsive Nanoparticles for Anti-tumor Drug Delivery. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00647"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4731","DOI":"10.1021\/acsbiomaterials.9b01979","article-title":"Ultrasound-Responsive Carriers for Therapeutic Applications","volume":"6","author":"Chandan","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"454","DOI":"10.2174\/0929867323666160813211736","article-title":"Design and Fabrication of Magnetically Responsive Nanocarriers for Drug Delivery","volume":"24","author":"Kralj","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1002\/(SICI)1097-4636(19991215)47:4<595::AID-JBM17>3.0.CO;2-I","article-title":"A pH- and ionic strength-responsive polypeptide hydrogel: Synthesis, characterization, and preliminary protein release studies","volume":"47","author":"Markland","year":"1999","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ijbiomac.2015.05.011","article-title":"Synthesis of pH- and ionic strength-responsive microgels and their interactions with lysozyme","volume":"79","author":"Zhang","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00424-024-03025-9","article-title":"Physiological regulation of oral saliva ion composition and flow rate are not coupled in healthy humans-Partial revision of our current knowledge required","volume":"477","author":"Schwerdt","year":"2025","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.clinbiochem.2016.06.001","article-title":"Basic concepts and practical equations on osmolality: Biochemical approach","volume":"49","author":"Rasouli","year":"2016","journal-title":"Clin. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.tifs.2020.11.004","article-title":"Lysozyme and its modified forms: A critical appraisal of selected properties and potential","volume":"107","author":"Yang","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102174","DOI":"10.1016\/j.jddst.2020.102174","article-title":"Ethanol injection technique for liposomes formulation: An insight into development, influencing factors, challenges and applications","volume":"61","author":"Gouda","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hassan, A.A.A., Sovany, T., Pamlenyi, K., Deak, M., Hornok, V., Csapo, E., Regdon, G., Csoka, I., and Kristo, K. (2024). QbD Approach-Based Preparation and Optimization of Hydrophobic Ion-Pairing Complex of Lysozyme with Sodium Dodecyl Sulphate to Enhance Stability in Lipid-Based Carriers. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16050589"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.fjps.2017.02.001","article-title":"Pharmaceutical significance of Eudragit: A review","volume":"3","author":"Patra","year":"2017","journal-title":"Future J. Pharm. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1021\/jp983852i","article-title":"Lysozyme net charge and ion binding in concentrated aqueous electrolyte solutions","volume":"103","author":"Kuehner","year":"1999","journal-title":"J. Phys. Chem. B"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"148","DOI":"10.4103\/0975-7406.111821","article-title":"Thermal stability of high concentration lysozyme across varying pH: A Fourier Transform Infrared study","volume":"5","author":"Venkataramani","year":"2013","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gouda, A.E., Sakr, O.S., Nasr, M., and Sammour, O.A. (2026). Stepwise effects of formulation additives and process parameters on ethanol injection-prepared nanoliposomes for cancer delivery: A preformulation study. Sci. Rep.","DOI":"10.1038\/s41598-026-52869-x"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1080\/03639045.2016.1180392","article-title":"Lysozyme-loaded lipid-polymer hybrid nanoparticles: Preparation, characterization and colloidal stability evaluation","volume":"42","author":"Devrim","year":"2016","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"N36","DOI":"10.1111\/j.1750-3841.2009.01512.x","article-title":"Biopolymer nanoparticles from heat-treated electrostatic protein-polysaccharide complexes: Factors affecting particle characteristics","volume":"75","author":"Jones","year":"2010","journal-title":"J. Food Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0167-4838(89)90020-4","article-title":"Electrostatic interactions in proteins. A theoretical analysis of lysozyme ionization","volume":"999","author":"Spassov","year":"1989","journal-title":"Biochim. Biophys. Acta (BBA)-Protein Struct. Mol. Enzymol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/pat.5093","article-title":"Polymethylmethacrylate derivatives Eudragit E100 and L100: Interactions and complexation with surfactants","volume":"32","author":"Ofridam","year":"2021","journal-title":"Polym. Adv. Technol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Du, G., and Sun, X. (2023). Ethanol injection method for liposome preparation. Liposomes: Methods and Protocols, Humana.","DOI":"10.1007\/978-1-0716-2954-3_5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"346","DOI":"10.4103\/1735-5362.213979","article-title":"Factors affecting liposomes particle size prepared by ethanol injection method","volume":"12","author":"Shaker","year":"2017","journal-title":"Res. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.cherd.2010.09.018","article-title":"Analysis of process parameters on the characteristics of liposomes prepared by ethanol injection with a view to process scale-up: Effect of temperature and batch volume","volume":"89","author":"Justo","year":"2011","journal-title":"Chem. Eng. Res. Des."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3109\/08982104.2012.717298","article-title":"Modified and derived ethanol injection toward liposomes: Development of the process","volume":"23","author":"Gentine","year":"2013","journal-title":"J. Liposome Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0378-5173(93)90389-W","article-title":"Liposomes obtained by the ethanol injection method","volume":"95","author":"Pons","year":"1993","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1081\/LPR-120039794","article-title":"Novel camptothecin analogue (gimatecan)-containing liposomes prepared by the ethanol injection method","volume":"14","author":"Stano","year":"2004","journal-title":"J. Liposome Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3109\/08982104.2011.584319","article-title":"Fast high-throughput screening of temoporfin-loaded liposomal formulations prepared by ethanol injection method","volume":"22","author":"Yang","year":"2012","journal-title":"J. Liposome Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fbio.2016.04.005","article-title":"Effect of composition, hydrogenation of phospholipids and lyophilization on the characteristics of eugenol-loaded liposomes prepared by ethanol injection method","volume":"15","author":"Sebaaly","year":"2016","journal-title":"Food Biosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"119794","DOI":"10.1016\/j.ijpharm.2020.119794","article-title":"Optimization of the synthetic parameters of lipid polymer hybrid nanoparticles dual loaded with darunavir and ritonavir for the treatment of HIV","volume":"588","author":"Elkateb","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1517\/17425247.2016.1165662","article-title":"Strategies for optimizing polymer-lipid hybrid nanoparticle-mediated drug delivery","volume":"13","author":"Wu","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105737","DOI":"10.1016\/j.ejps.2021.105737","article-title":"Sodium glycodeoxycholate and sodium deoxycholate as epithelial permeation enhancers: In vitro and ex vivo intestinal and buccal bioassays","volume":"159","author":"Brayden","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1517\/17425240903338758","article-title":"Chemical permeation enhancers for transbuccal drug delivery","volume":"7","author":"Hassan","year":"2010","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1021\/bm025664a","article-title":"Ionic strength dependence of protein-polyelectrolyte interactions","volume":"4","author":"Seyrek","year":"2003","journal-title":"Biomacromolecules"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3897\/pharmacia.71.e116917","article-title":"Evaluation of types and concentration of bile salts impact on physical properties of nisoldipine-loaded bilosomes","volume":"71","author":"Naji","year":"2024","journal-title":"Pharmacia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.colsurfb.2014.02.036","article-title":"Storage stability and skin permeation of vitamin C liposomes improved by pectin coating","volume":"117","author":"Zhou","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8175","DOI":"10.1021\/jf402085f","article-title":"Liposomes as Vehicles for Lutein: Preparation, Stability, Liposomal Membrane Dynamics, and Structure","volume":"61","author":"Tan","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s11094-020-02100-6","article-title":"Design and Physicochemical Characterization of Lysozyme Loaded Niosomal Formulations as a New Controlled Delivery System","volume":"53","author":"Sadeghi","year":"2020","journal-title":"Pharm. Chem. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.carbpol.2016.08.076","article-title":"Integration of lysozyme into chitosan nanoparticles for improving antibacterial activity","volume":"155","author":"Wu","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.foodchem.2017.01.073","article-title":"Lysozyme distribution, structural identification, and in vitro release of starch-based microgel-lysozyme complexes","volume":"227","author":"Zhang","year":"2017","journal-title":"Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"\u0160ahinovi\u0107, M., Hassan, A., Krist\u00f3, K., Regdon, G., Vrani\u0107, E., and Sov\u00e1ny, T. (2023). Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030995"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/6\/719\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:59:48Z","timestamp":1781675988000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/6\/719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":57,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pharmaceutics18060719"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18060719","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]}}}