{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T11:03:24Z","timestamp":1761649404946,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Poland","award":["SKN\/SP\/568478\/2023","APVV-22-0133"],"award-info":[{"award-number":["SKN\/SP\/568478\/2023","APVV-22-0133"]}]},{"name":"Slovak Research and Development Agency","award":["SKN\/SP\/568478\/2023","APVV-22-0133"],"award-info":[{"award-number":["SKN\/SP\/568478\/2023","APVV-22-0133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Restoring the structures and functions of tissues along with organs in human bodies is a topic gathering attention nowadays. These issues are widely discussed in the context of regenerative medicine. Excipients\/delivery systems play a key role in this topic, guaranteeing a positive impact on the effectiveness of the drugs or therapeutic substances supplied. Advances in materials engineering, particularly in the development of hydrogel biomaterials, have influenced the idea of creating an innovative material that could serve as a carrier for active substances while ensuring biocompatibility and meeting all the stringent requirements imposed on medical materials. This work presents the preparation of a natural polymeric material based on pullulan modified with silymarin, which belongs to the group of flavonoids and derives from a plant called Silybum marianum. Under UV light, matrices with a previously prepared composition were crosslinked. Before proceeding to the next stage of the research, the purity of the composition of the matrices was checked using Fourier-transform infrared (FT-IR) spectroscopy. Incubation tests lasting 19 days were carried out using incubation fluids such as simulated body fluid (SBF), Ringer\u2019s solution, and artificial saliva. Changes in pH, electrolytic conductivity, and weight were observed and then used to determine the sorption capacity. During incubation, SBF proved to be the most stable fluid, with a pH level of 7.6\u20137.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer\u2019s solution and artificial saliva (approximately 350%) and SBF (approximately 300%). After incubation, the surface morphology was analyzed using an optical microscope for samples demonstrating the greatest changes over time. The active substance, silymarin, was released using a water bath, and then the antioxidant capacity was determined using the Folin\u2013Cioc\u00e2lteu test. The tests carried out proved that the material produced is active and harmless, which was shown by the incubation analysis. The continuous release of the active ingredient increases the biological value of the biomaterial. The material requires further research, including a more detailed assessment of its balance; however, it demonstrates promising potential for further experiments.<\/jats:p>","DOI":"10.3390\/ijms25189972","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T01:52:31Z","timestamp":1726624351000},"page":"9972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polyethylene Glycol\/Pullulan-Based Carrier for Silymarin Delivery and Its Potential in Biomedical Applications"],"prefix":"10.3390","volume":"25","author":[{"given":"Julia","family":"Iwaniec","sequence":"first","affiliation":[{"name":"Cracow University of Technology, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-3478","authenticated-orcid":false,"given":"Karina","family":"Nizio\u0142ek","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, CUT Doctoral School, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patryk","family":"Polanowski","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8570-3594","authenticated-orcid":false,"given":"Dagmara","family":"S\u0142ota","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, CUT Doctoral School, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edyta","family":"Kosi\u0144ska","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, CUT Doctoral School, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Sadlik","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, CUT Doctoral School, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3799-6887","authenticated-orcid":false,"given":"Krzysztof","family":"Miernik","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-9052","authenticated-orcid":false,"given":"Josef","family":"Jampilek","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia"},{"name":"Department of Chemical Biology, Faculty of Science, Palacky University Olomouc, Slechtitelu 27, 783 71 Olomouc, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0005-6146","authenticated-orcid":false,"given":"Agnieszka","family":"Sobczak-Kupiec","sequence":"additional","affiliation":[{"name":"Cracow University of Technology, Faculty of Materials Engineering and Physics, Department of Materials Science, 37 Jana Paw\u0142a II Av., 31-864 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Paolino, D., Sinha, P., Fresta, M., and Ferrari, M. (2006). Drug Delivery Systems. Encyclopedia of Medical Devices and Instrumentation, John Wiley and Sons, Inc.","DOI":"10.1002\/0471732877.emd274"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/2230-973X.96920","article-title":"Drug Delivery Systems: An Updated Review","volume":"2","author":"Tiwari","year":"2012","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1146\/annurev-chembioeng-073009-100847","article-title":"Polymers for Drug Delivery Systems","volume":"1","author":"Liechty","year":"2010","journal-title":"Annu. Rev. Chem. Biomol. Eng."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.addr.2016.07.004","article-title":"Poly(Lactic Acid) Based Hydrogels","volume":"107","author":"Basu","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"024003","DOI":"10.1088\/2053-1591\/acb98e","article-title":"Freeze-Thaw Hydrogel Fabrication Method: Basic Principles, Synthesis Parameters, Properties, and Biomedical Applications","volume":"10","author":"Waresindo","year":"2023","journal-title":"Mater. Res. Express"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10576","DOI":"10.1021\/acs.macromol.2c01469","article-title":"Roadmap to Design Mechanically Robust Copolymer Hydrogels Naturally Cross-Linked by Hydrogen Bonds","volume":"55","author":"Erkoc","year":"2022","journal-title":"Macromolecules"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chai, Q., Jiao, Y., and Yu, X. (2017). Hydrogels for Biomedical Applications: Their Characteristics and the Mechanisms behind Them. Gels, 3.","DOI":"10.3390\/gels3010006"},{"key":"ref_8","first-page":"369","article-title":"Recent Advances in Polymeric Drug Delivery Carrier Systems","volume":"10","author":"Sharma","year":"2018","journal-title":"Adv. Polym. Biomed. Appl."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1002\/aic.10489","article-title":"Integrated Medical Feedback Systems for Drug Delivery","volume":"51","author":"Heller","year":"2005","journal-title":"AIChE J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.ijbiomac.2020.10.227","article-title":"Pullulan in Biomedical Research and Development\u2014A Review","volume":"166","author":"Singh","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Singh, R.S., Kaur, N., Singh, D., Purewal, S.S., and Kennedy, J.F. (2023). Pullulan in Pharmaceutical and Cosmeceutical Formulations: A Review. Int. J. Biol. Macromol., 231.","DOI":"10.1016\/j.ijbiomac.2023.123353"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1080\/10717544.2022.2144544","article-title":"Pullulan Based Derivatives: Synthesis, Enhanced Physicochemical Properties, and Applications","volume":"29","author":"Agrawal","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00253-011-3477-y","article-title":"Pullulan: Biosynthesis, Production, and Applications","volume":"92","author":"Cheng","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105066","DOI":"10.1016\/j.jddst.2023.105066","article-title":"Pullulan Hydrogels as Drug Release Platforms in Biomedicine","volume":"89","author":"Teixeira","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.ijbiomac.2021.07.068","article-title":"Efficient Pullulan Production by Aureobasidium Pullulans Using Cost-Effective Substrates","volume":"186","author":"He","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","first-page":"100115","article-title":"A Review on Anticancer Applications of Pullulan and Pullulan Derivative Nanoparticles","volume":"2","author":"Ganie","year":"2021","journal-title":"Carbohydr. Polym. Technol. Appl."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sun, S., Cui, Y., Yuan, B., Dou, M., Wang, G., Xu, H., Wang, J., Yin, W., Wu, D., and Peng, C. (2023). Drug Delivery Systems Based on Polyethylene Glycol Hydrogels for Enhanced Bone Regeneration. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1117647"},{"key":"ref_18","first-page":"369","article-title":"Flawonoidy w Profilaktyce i Terapii","volume":"65","author":"Majewska","year":"2009","journal-title":"Farm. Pol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kopustinskiene, D.M., Jakstas, V., Savickas, A., and Bernatoniene, J. (2020). Flavonoids as Anticancer Agents. Nutrients, 12.","DOI":"10.3390\/nu12020457"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.26881\/tutg.2021.3.05","article-title":"Moda Na Flawonoidy-o Co Tyle Szumu?","volume":"6","author":"Maciejewska","year":"2021","journal-title":"Tutoring Gedanensis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1080\/14786419.2018.1493588","article-title":"Flavonoids: Biological Activities and Therapeutic Potential","volume":"34","author":"Mesquita","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s43094-020-00161-8","article-title":"Flavonoids as Natural Phenolic Compounds and Their Role in Therapeutics: An Overview","volume":"7","author":"Mutha","year":"2021","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jan, S., and Abbas, N. (2018). Chemistry of Himalayan Phytochemicals. Himalayan Phytochemicals, Elsevier.","DOI":"10.1016\/B978-0-08-102227-6.00004-8"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s43088-020-00065-9","article-title":"Flavonoids: Isolation, Characterization, and Health Benefits","volume":"9","author":"Ekalu","year":"2020","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ninfali, P., Antonelli, A., Magnani, M., and Scarpa, E.S. (2020). Antiviral Properties of Flavonoids and Delivery Strategies. Nutrients, 12.","DOI":"10.3390\/nu12092534"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1056\/NEJMp058291","article-title":"Oseltamivir Resistance\u2014Disabling Our Influenza Defenses","volume":"353","author":"Moscona","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fan, X., Fan, Z., Yang, Z., Huang, T., Tong, Y., Yang, D., Mao, X., and Yang, M. (2022). Flavonoids\u2014Natural Gifts to Promote Health and Longevity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042176"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1186\/s12967-023-04321-1","article-title":"Dietary Flavonoids Intake Contributes to Delay Biological Aging Process: Analysis from NHANES Dataset","volume":"21","author":"Xing","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_29","first-page":"623","article-title":"Antioxidant and Anti-Aging Activities of Silybum Marianum Protein Hydrolysate in Mice Treated with D-Galactose","volume":"30","author":"Zhu","year":"2017","journal-title":"Biomed. Environ. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"465","DOI":"10.2165\/00063030-200115070-00005","article-title":"Silymarin: A Review of Its Clinical Properties in the Management of Hepatic Disorders","volume":"15","author":"Wellington","year":"2001","journal-title":"BioDrugs"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.canlet.2008.03.053","article-title":"Multitargeted Therapy of Cancer by Silymarin","volume":"269","author":"Ramasamy","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20190206","DOI":"10.1515\/jbcpp-2019-0206","article-title":"Silymarin: Not Just Another Antioxidant","volume":"31","author":"Camini","year":"2020","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_33","first-page":"75","article-title":"Pharmacological, Biochemical and Therapeutic Potential of Milk Thistle (Silymarin): A Review","volume":"37","author":"Adetuyi","year":"2021","journal-title":"World News Nat. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3390\/antiox4010204","article-title":"Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives","volume":"4","author":"Surai","year":"2015","journal-title":"Antioxidants"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"153320","DOI":"10.1016\/j.phymed.2020.153320","article-title":"Silymarin and Neurodegenerative Diseases: Therapeutic Potential and Basic Molecular Mechanisms","volume":"79","author":"Haddadi","year":"2020","journal-title":"Phytomedicine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.2165\/00003495-200161140-00003","article-title":"The Use of Silymarin in the Treatment of Liver Diseases","volume":"61","author":"Saller","year":"2001","journal-title":"Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Surai, P.F., Surai, A., and Earle-Payne, K. (2024). Silymarin and Inflammation: Food for Thoughts. Antioxidants, 13.","DOI":"10.3390\/antiox13010098"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Elangwe, C.N., Morozkina, S.N., Olekhnovich, R.O., Polyakova, V.O., Krasichkov, A., Yablonskiy, P.K., and Uspenskaya, M.V. (2023). Pullulan-Based Hydrogels in Wound Healing and Skin Tissue Engineering Applications: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054962"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.ijbiomac.2022.07.114","article-title":"Silymarin Nanocrystals-Laden Chondroitin Sulphate-Based Thermoreversible Hydrogels; A Promising Approach for Bioavailability Enhancement","volume":"218","author":"Jabeen","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1080\/17425247.2016.1182485","article-title":"Polyethylene Glycol (PEG): A Versatile Polymer for Pharmaceutical Applications","volume":"13","author":"Shegokar","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10748","DOI":"10.1039\/D1NR02065J","article-title":"Effects of Polyethylene Glycol on the Surface of Nanoparticles for Targeted Drug Delivery","volume":"13","author":"Shi","year":"2021","journal-title":"Nanoscale"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14022","DOI":"10.1021\/acsnano.1c05922","article-title":"Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies","volume":"15","author":"Chen","year":"2021","journal-title":"ACS Nano"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lu\u00eds, \u00c2., Ramos, A., and Domingues, F. (2020). Pullulan Films Containing Rockrose Essential Oil for Potential Food Packaging Applications. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100681"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sahu, M., Reddy, V.R.M., Kim, B., Patro, B., Park, C., Kim, W.K., and Sharma, P. (2022). Fabrication of Cu2ZnSnS4 Light Absorber Using a Cost-Effective Mechanochemical Method for Photovoltaic Applications. Materials, 15.","DOI":"10.3390\/ma15051708"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1146\/annurev.med.58.082405.095329","article-title":"Progress and Potential for Regenerative Medicine","volume":"58","author":"Gurtner","year":"2007","journal-title":"Annu. Rev. Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"S\u0142ota, D., Florkiewicz, W., Pi\u0119tak, K., Szwed, A., W\u0142odarczyk, M., Siwi\u0144ska, M., Rudnicka, K., and Sobczak-Kupiec, A. (2021). Preparation, Characterization, and Biocompatibility Assessment of Polymer-Ceramic Composites Loaded with Salvia Officinalis Extract. Materials, 14.","DOI":"10.3390\/ma14206000"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1007\/s10311-019-00862-4","article-title":"Drug Delivery Systems Using Pullulan, a Biocompatible Polysaccharide Produced by Fungal Fermentation of Starch","volume":"17","author":"Grigoras","year":"2019","journal-title":"Environ. Chem. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jpedsurg.2011.10.013","article-title":"Regenerative Medicine Strategies","volume":"47","author":"Atala","year":"2012","journal-title":"J. Pediatr. Surg."},{"key":"ref_49","unstructured":"Singh, R.S., and Saini, G.K. (2016). Chapter 15 Pullulan as Th Erapeutic Tool in Biomedical Applications. Advances in Industrial Biotechnology, IK International Publishing House Pvt. Ltd."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/os.12637","article-title":"Optical Microscopy and Electron Microscopy for the Morphological Evaluation of Tendons: A Mini Review","volume":"12","author":"Xu","year":"2020","journal-title":"Orthop. Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9972\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:57:22Z","timestamp":1760111842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/18\/9972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,16]]},"references-count":50,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25189972"],"URL":"https:\/\/doi.org\/10.3390\/ijms25189972","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,9,16]]}}}