{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:29:29Z","timestamp":1780403369513,"version":"3.54.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000308","name":"British Council","doi-asserted-by":"publisher","award":["Patient-tailored biomaterials for tissue regeneration, combating microbial contamination and drug delivery"],"award-info":[{"award-number":["Patient-tailored biomaterials for tissue regeneration, combating microbial contamination and drug delivery"]}],"id":[{"id":"10.13039\/501100000308","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"RUSSIAN SCIENCE FOUNDATION","doi-asserted-by":"publisher","award":["19-75-10043"],"award-info":[{"award-number":["19-75-10043"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>A novel versatile biocompatible hydrogel of whey protein isolate (WPI) and two types of tannic acid (TAs) was prepared by crosslinking of WPI with TAs in a one-step method at high temperature for 30 min. WPI is one common protein-based preparation which is used for hydrogel formation. The obtained WPI-TA hydrogels were in disc form and retained their integrity after sterilization by autoclaving. Two TA preparations of differing molecular weight and chemical structure were compared, namely a polygalloyl glucose-rich extract-ALSOK 02-and a polygalloyl quinic acid-rich extract-ALSOK 04. Hydrogel formation was observed for WPI solutions containing both preparations. The swelling characteristics of hydrogels were investigated at room temperature at different pH values, namely 5, 7, and 9. The swelling ability of hydrogels was independent of the chemical structure of the added TAs. A trend of decrease of mass increase (MI) in hydrogels was observed with an increase in the TA\/WPI ratio compared to the control WPI hydrogel without TA. This dependence (a MI decrease-TA\/WPI ratio) was observed for hydrogels with different types of TA both in neutral and acidic conditions (pH 5.7). Under alkaline conditions (pH 9), negative values of swelling were observed for all hydrogels with a high content of TAs and were accompanied by a significant release of TAs from the hydrogel network. Our studies have shown that the release of TA from hydrogels containing ALSOK04 is higher than from hydrogels containing ALSOK 02. Moreover, the addition of TAs, which display a strong anti-cancer effect, increases the cytotoxicity of WPI-TAs hydrogels against the Hep-2 human laryngeal squamous carcinoma (Hep-2 cells) cell line. Thus, WPI-TA hydrogels with prolonged drug release properties and cytotoxicity effect can be used as anti-cancer scaffolds.<\/jats:p>","DOI":"10.3390\/ma14040749","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T14:04:13Z","timestamp":1612706653000},"page":"749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["pH-Sensitive Dairy-Derived Hydrogels with a Prolonged Drug Release Profile for Cancer Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-3947","authenticated-orcid":false,"given":"Oksana A.","family":"Mayorova","sequence":"first","affiliation":[{"name":"Institute of Nanostructures and Biosystems, Saratov State University, 83 Astrakhanskaya st., 410012 Saratov, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben C. N.","family":"Jolly","sequence":"additional","affiliation":[{"name":"Engineering Department, Lancaster University, Gillow Av., Lancaster LA1 4YW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman A.","family":"Verkhovskii","sequence":"additional","affiliation":[{"name":"Institute of Nanostructures and Biosystems, Saratov State University, 83 Astrakhanskaya st., 410012 Saratov, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina O.","family":"Plastun","sequence":"additional","affiliation":[{"name":"Institute of Nanostructures and Biosystems, Saratov State University, 83 Astrakhanskaya st., 410012 Saratov, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5288-4157","authenticated-orcid":false,"given":"Olga A.","family":"Sindeeva","sequence":"additional","affiliation":[{"name":"Institute of Nanostructures and Biosystems, Saratov State University, 83 Astrakhanskaya st., 410012 Saratov, Russia"},{"name":"Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Building 3, 143026 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E. L.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Engineering Department, Lancaster University, Gillow Av., Lancaster LA1 4YW, UK"},{"name":"Materials Science Institute (MSI), Lancaster University, Gillow Av., Lancaster LA1 4YW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108408","DOI":"10.1016\/j.matdes.2019.108408","article-title":"Novel naturally derived whey protein isolate and aragonite biocomposite hydrogels have potential for bone regeneration","volume":"188","author":"Gupta","year":"2020","journal-title":"Mater. Des."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Norris, K., Kocot, M., Tryba, A.M., Chai, F., Talari, A., Ashton, L., Parakhonskiy, B.V., Samal, S.K., Blanchemain, N., and Pamu\u0142a, E. (2020). Marine-Inspired Enzymatic Mineralization of Dairy-Derived Whey Protein Isolate (WPI) Hydrogels for Bone Tissue Regeneration. Mar. Drugs, 18.","DOI":"10.3390\/md18060294"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"127115","DOI":"10.1016\/j.matlet.2019.127115","article-title":"Novel whey protein isolate-based highly porous scaffolds modified with therapeutic ion-releasing bioactive glasses","volume":"261","author":"Dziadek","year":"2020","journal-title":"Mater. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1002\/jbm.a.36754","article-title":"Novel multicomponent organic\u2013inorganic WPI\/gelatin\/CaP hydrogel composites for bone tissue engineering","volume":"107","author":"Dziadek","year":"2019","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1051\/lait:2006008","article-title":"A comparative study of the gelation properties of whey protein concentrate and whey protein isolate","volume":"86","author":"Lorenzen","year":"2006","journal-title":"Lait"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3168\/jds.2017-13119","article-title":"Application of whey protein isolate in bone regeneration: Effects on growth and osteogenic differentiation of bone-forming cells","volume":"101","author":"Douglas","year":"2018","journal-title":"J. Dairy Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.foodhyd.2017.04.031","article-title":"Polysaccharide blended whey protein isolate-(WPI) hydrogels: A physicochemical and controlled release study","volume":"71","author":"Ozel","year":"2017","journal-title":"Food Hydrocoll."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Andoyo, R., Lestari, V.D., Mardawati, E., and Nurhadi, B. (2018). Fractal Dimension Analysis of Texture Formation of Whey Protein-Based Foods. Int. J. Food Sci., 2018.","DOI":"10.1155\/2018\/7673259"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., and Chi-leung HUI, P. (2019). Review of Stimuli-Responsive Polymers in Drug Delivery and Textile Application. Molecules, 24.","DOI":"10.3390\/molecules24142547"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Jourdes, M., Pouys\u00e9gu, L., Deffieux, D., Teissedre, P.L., and Quideau, S. (2013). Hydrolyzable tannins: Gallotannins and ellagitannins. Natural Products: Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes, Springer.","DOI":"10.1007\/978-3-642-22144-6_65"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ky, I., Le Floch, A., Zeng, L., Pechamat, L., Jourdes, M., and Teissedre, P.L. (2015). Tannins. Encyclopedia of Food and Health, Elsevier.","DOI":"10.1016\/B978-0-12-384947-2.00683-8"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1900073","DOI":"10.1002\/macp.201900073","article-title":"Tannic Acid-Inspired Star-Like Macromolecules via Temporally Controlled Multi-Step Potential Electrolysis","volume":"220","author":"Zaborniak","year":"2019","journal-title":"Macromol. Chem. Phys."},{"key":"ref_13","first-page":"3645","article-title":"Structural requirements for stabilization of vascular elastin by polyphenolic tannins","volume":"27","author":"Isenburg","year":"2006","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1021\/bm501623c","article-title":"Tea Stains-Inspired Initiator Primer for Surface Grafting of Antifouling and Antimicrobial Polymer Brush Coatings","volume":"16","author":"Pranantyo","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chai, Y., Lee, H.J., Shaik, A.A., Nkhata, K., Xing, C., Zhang, J., Jeong, S.J., Kim, S.H., and L\u00fc, J. (2010). Penta-O-galloyl-\u03b2-D-glucose induces G1arrest and DNA replicative S-phase arrest independently of P21 cyclin-dependent kinase inhibitor 1A, P27 cyclin-dependent kinase inhibitor 1B and P53 in human breast cancer cells and is orally active against triple-negative xenograft growth. Breast Cancer Res., 12.","DOI":"10.1186\/bcr2634"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"He, J., Dong, Y., Liu, X., Wan, Y., Gu, T., Zhou, X., and Liu, M. (2019). Comparison of Chemical Compositions, Antioxidant, and Anti-Photoaging Activities of Paeonia suffruticosa Flowers at Different Flowering Stages. Antioxidants, 8.","DOI":"10.3390\/antiox8090345"},{"key":"ref_17","first-page":"1736","article-title":"Proteomic analysis of the effect of the polyphenol pentagalloyl glucose on proteins involved in neurodegenerative diseases in activated BV-2 microglial cells","volume":"20","author":"Mendonca","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1080\/09205063.2017.1421349","article-title":"Anticancer efficacy of tannic acid is dependent on the stiffness of the underlying matrix","volume":"29","author":"Bridgeman","year":"2018","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1021\/acsabm.8b00690","article-title":"Ternary Composite Nanofibers Containing Chondroitin Sulfate Scavenge Inflammatory Chemokines from Solution and Prohibit Squamous Cell Carcinoma Migration","volume":"2","author":"Boyle","year":"2019","journal-title":"ACS Appl. Bio. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115147","DOI":"10.1016\/j.carbpol.2019.115147","article-title":"Rapid self-healing, stretchable, moldable, antioxidant and antibacterial tannic acid-cellulose nanofibril composite hydrogels","volume":"224","author":"Ge","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Seczyk, L., Swieca, M., Kapusta, I., and Gawlik-Dziki, U. (2019). Protein\u2013phenolic interactions as a factor affecting the physicochemical properties of white bean proteins. Molecules, 24.","DOI":"10.3390\/molecules24030408"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Douglas, T.E.L., Keppler, J.K., Vandrovcov\u00e1, M., Plencner, M., Beranov\u00e1, J., Feuereisen, M., Parakhonskiy, B.V., Svenskaya, Y., Atkin, V., and Ivanova, A. (2020). Enhancement of Biomimetic Enzymatic Mineralization of Gellan Gum Polysaccharide Hydrogels by Plant-Derived Gallotannins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072315"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000494732","article-title":"Whey Protein Complexes with Green Tea Polyphenols: Antimicrobial, Osteoblast-Stimulatory, and Antioxidant Activities","volume":"206","author":"Carson","year":"2018","journal-title":"Cells Tissues Organs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/9780470110171.ch2","article-title":"Analysis of phenolic compounds of interest in metabolism","volume":"1","author":"Bray","year":"1954","journal-title":"Methods Biochem. Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0165-0270(99)00062-X","article-title":"A new Alamar Blue viability assay to rapidly quantify oligodendrocyte death","volume":"91","author":"Back","year":"1999","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4097\/kjae.2017.70.3.267","article-title":"Statistical data presentation","volume":"70","author":"In","year":"2017","journal-title":"Korean J. Anesthesiol."},{"key":"ref_27","first-page":"1285","article-title":"Remodeling of tannic acid crosslinked collagen type I induces apoptosis in ER+ breast cancer cells","volume":"35","author":"Ngobili","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2174\/1871520616666151111115809","article-title":"Tannic Acid Inhibits Proliferation, Migration, Invasion of Prostate Cancer and Modulates Drug Metabolizing and Antioxidant Enzymes","volume":"16","author":"Karakurt","year":"2016","journal-title":"Anticancer. Agents Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wang, C.-C., Chen, H.-F., Wu, J.-Y., and Chen, L.-G. (2019). Stability of Principal Hydrolysable Tannins from Trapa taiwanensis Hulls. Molecules, 24.","DOI":"10.3390\/molecules24020365"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1039\/c2sm06976h","article-title":"Swelling behaviour, charge and mesh size of thermal protein hydrogels as influenced by pH during gelation","volume":"8","author":"Betz","year":"2012","journal-title":"Soft Matter."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.lwt.2015.10.054","article-title":"Effect of covalent modification by (-)-epigallocatechin-3-gallate on physicochemical and functional properties of whey protein isolate","volume":"66","author":"Jia","year":"2016","journal-title":"LWT Food Sci. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3109\/10409239509085140","article-title":"The use and misuse of FTIR spectroscopy in the determination of protein structure","volume":"30","author":"Jackson","year":"1995","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.foodres.2015.08.024","article-title":"Study of the interactions between rosmarinic acid and bovine milk whey protein \u03b1-Lactalbumin, \u03b2-Lactoglobulin and Lactoferrin","volume":"77","author":"Ferraro","year":"2015","journal-title":"Food Res. Int."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, C., Zhou, X., Wang, H., Sun, X., and Guo, M. (2019). Interactions between \u03b2-Lactoglobulin and 3,3\u2032-Diindolylmethane in Model System. Molecules, 24.","DOI":"10.3390\/molecules24112151"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"052501","DOI":"10.1103\/PhysRevE.99.052501","article-title":"Solvent self-diffusion dependence on the swelling degree of a hydrogel","volume":"99","author":"Barros","year":"2019","journal-title":"Phys. Rev. E"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ijpharm.2006.03.032","article-title":"Controlled release of doxorubicin from thermosensitive poly(organophosphazene) hydrogels","volume":"319","author":"Kang","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109985","DOI":"10.1016\/j.msec.2019.109985","article-title":"Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regeneration","volume":"105","author":"Barros","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.foodres.2013.02.009","article-title":"A review on protein-phenolic interactions and associated changes","volume":"51","author":"Ozdal","year":"2013","journal-title":"Food Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/10408398.2010.499808","article-title":"Interactions between polyphenols and macromolecules: Quantification methods and mechanisms","volume":"52","author":"Renard","year":"2012","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jfoodeng.2006.11.001","article-title":"Use of whey proteins for encapsulation and controlled delivery applications","volume":"83","author":"Gunasekaran","year":"2007","journal-title":"J. Food Eng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.foodchem.2018.06.015","article-title":"The effect of non-covalent interaction of chlorogenic acid with whey protein and casein on physicochemical and radical-scavenging activity of in vitro protein digests","volume":"268","author":"Jiang","year":"2018","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fphys.2013.00370","article-title":"pH sensing and regulation in cancer","volume":"4","author":"Damaghi","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00204-017-2021-y","article-title":"Regulation of SIRT1\/AMPK axis is critically involved in gallotannin-induced senescence and impaired autophagy leading to cell death in hepatocellular carcinoma cells","volume":"92","author":"Kwon","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1002\/ptr.5371","article-title":"Inhibition of Myeloid Cell Leukemia 1 and Activation of Caspases Are Critically Involved in Gallotannin-induced Apoptosis in Prostate Cancer Cells","volume":"29","author":"Park","year":"2015","journal-title":"Phyther. Res."}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/14\/4\/749\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:18Z","timestamp":1760160018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/14\/4\/749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ma14040749"],"URL":"https:\/\/doi.org\/10.3390\/ma14040749","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]}}}