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's 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 7.6-7.8. Sorption tests showed a high sorption capacity of samples incubated in both Ringer's 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-Ciocâlteu 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.

Cracow University of Technology CUT Doctoral School Faculty of Materials Engineering and Physics Department of Materials Science 37 Jana Pawła 2 Av 31 864 Krakow Poland

Cracow University of Technology Faculty of Materials Engineering and Physics Department of Materials Science 37 Jana Pawła 2 Av 31 864 Krakow Poland

Department of Analytical Chemistry Faculty of Natural Sciences Comenius University Ilkovicova 6 842 15 Bratislava Slovakia

Department of Chemical Biology Faculty of Science Palacky University Olomouc Slechtitelu 27 783 71 Olomouc Czech Republic

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Paolino D., Sinha P., Fresta M., Ferrari M. Encyclopedia of Medical Devices and Instrumentation. John Wiley and Sons, Inc.; Hoboken, NJ, USA: 2006. Drug Delivery Systems.

Tiwari G., Tiwari R., Bannerjee S., Bhati L., Pandey S., Pandey P., Sriwastawa B. Drug Delivery Systems: An Updated Review. Int. J. Pharm. Investig. 2012;2:2. doi: 10.4103/2230-973X.96920. PubMed DOI PMC

Liechty W.B., Kryscio D.R., Slaughter B.V., Peppas N.A. Polymers for Drug Delivery Systems. Annu. Rev. Chem. Biomol. Eng. 2010;1:149–173. doi: 10.1146/annurev-chembioeng-073009-100847. PubMed DOI PMC

Basu A., Kunduru K.R., Doppalapudi S., Domb A.J., Khan W. Poly(Lactic Acid) Based Hydrogels. Adv. Drug Deliv. Rev. 2016;107:192–205. doi: 10.1016/j.addr.2016.07.004. PubMed DOI

Waresindo W.X., Luthfianti H.R., Priyanto A., Hapidin D.A., Edikresnha D., Aimon A.H., Suciati T., Khairurrijal K. Freeze-Thaw Hydrogel Fabrication Method: Basic Principles, Synthesis Parameters, Properties, and Biomedical Applications. Mater. Res. Express. 2023;10:024003. doi: 10.1088/2053-1591/acb98e. DOI

Erkoc C., Yildirim E., Yurtsever M., Okay O. Roadmap to Design Mechanically Robust Copolymer Hydrogels Naturally Cross-Linked by Hydrogen Bonds. Macromolecules. 2022;55:10576–10589. doi: 10.1021/acs.macromol.2c01469. DOI

Chai Q., Jiao Y., Yu X. Hydrogels for Biomedical Applications: Their Characteristics and the Mechanisms behind Them. Gels. 2017;3:6. doi: 10.3390/gels3010006. PubMed DOI PMC

Sharma P., Negi P., Mahindroo N. Recent Advances in Polymeric Drug Delivery Carrier Systems. Adv. Polym. Biomed. Appl. 2018;10:369–388.

Heller A. Integrated Medical Feedback Systems for Drug Delivery. AIChE J. 2005;51:1054–1066. doi: 10.1002/aic.10489. DOI

Singh R.S., Kaur N., Hassan M., Kennedy J.F. Pullulan in Biomedical Research and Development—A Review. Int. J. Biol. Macromol. 2021;166:694–706. doi: 10.1016/j.ijbiomac.2020.10.227. PubMed DOI

Singh R.S., Kaur N., Singh D., Purewal S.S., Kennedy J.F. Pullulan in Pharmaceutical and Cosmeceutical Formulations: A Review. Int. J. Biol. Macromol. 2023;231:123353. doi: 10.1016/j.ijbiomac.2023.123353. PubMed DOI

Agrawal S., Budhwani D., Gurjar P., Telange D., Lambole V. Pullulan Based Derivatives: Synthesis, Enhanced Physicochemical Properties, and Applications. Drug Deliv. 2022;29:3328–3339. doi: 10.1080/10717544.2022.2144544. PubMed DOI PMC

Cheng K.C., Demirci A., Catchmark J.M. Pullulan: Biosynthesis, Production, and Applications. Appl. Microbiol. Biotechnol. 2011;92:29–44. doi: 10.1007/s00253-011-3477-y. PubMed DOI

Teixeira M.O., Marinho E., Silva C., Antunes J.C., Felgueiras H.P. Pullulan Hydrogels as Drug Release Platforms in Biomedicine. J. Drug Deliv. Sci. Technol. 2023;89:105066. doi: 10.1016/j.jddst.2023.105066. DOI

He C., Zhang Z., Zhang Y., Wang G., Wang C., Wang D., Wei G. Efficient Pullulan Production by Aureobasidium Pullulans Using Cost-Effective Substrates. Int. J. Biol. Macromol. 2021;186:544–553. doi: 10.1016/j.ijbiomac.2021.07.068. PubMed DOI

Ganie S.A., Rather L.J., Li Q. A Review on Anticancer Applications of Pullulan and Pullulan Derivative Nanoparticles. Carbohydr. Polym. Technol. Appl. 2021;2:100115. doi: 10.1016/j.carpta.2021.100115. DOI

Sun S., Cui Y., Yuan B., Dou M., Wang G., Xu H., Wang J., Yin W., Wu D., Peng C. Drug Delivery Systems Based on Polyethylene Glycol Hydrogels for Enhanced Bone Regeneration. Front. Bioeng. Biotechnol. 2023;11:1117647. doi: 10.3389/fbioe.2023.1117647. PubMed DOI PMC

Majewska M., Czeczot H. Flawonoidy w Profilaktyce i Terapii. Farm. Pol. 2009;65:369–377.

Kopustinskiene D.M., Jakstas V., Savickas A., Bernatoniene J. Flavonoids as Anticancer Agents. Nutrients. 2020;12:457. doi: 10.3390/nu12020457. PubMed DOI PMC

Maciejewska P., Skrzypczak N. Moda Na Flawonoidy-o Co Tyle Szumu? Tutoring Gedanensis. 2021;6:55–64. doi: 10.26881/tutg.2021.3.05. DOI

Jucá M.M., Cysne Filho F.M.S., de Almeida J.C., Mesquita D.D.S., Barriga J.R.D.M., Dias K.C.F., Barbosa T.M., Vasconcelos L.C., Leal L.K.A.M., Ribeiro J.E., et al. Flavonoids: Biological Activities and Therapeutic Potential. Nat. Prod. Res. 2020;34:692–705. doi: 10.1080/14786419.2018.1493588. PubMed DOI

Mutha R.E., Tatiya A.U., Surana S.J. Flavonoids as Natural Phenolic Compounds and Their Role in Therapeutics: An Overview. Futur. J. Pharm. Sci. 2021;7:25. doi: 10.1186/s43094-020-00161-8. PubMed DOI PMC

Jan S., Abbas N. Himalayan Phytochemicals. Elsevier; Amsterdam, The Netherlands: 2018. Chemistry of Himalayan Phytochemicals; pp. 121–166.

Ekalu A., Dama Habila J. Flavonoids: Isolation, Characterization, and Health Benefits. Beni-Suef Univ. J. Basic Appl. Sci. 2020;9:45. doi: 10.1186/s43088-020-00065-9. DOI

Ninfali P., Antonelli A., Magnani M., Scarpa E.S. Antiviral Properties of Flavonoids and Delivery Strategies. Nutrients. 2020;12:2534. doi: 10.3390/nu12092534. PubMed DOI PMC

Moscona A. Oseltamivir Resistance—Disabling Our Influenza Defenses. N. Engl. J. Med. 2005;353:2633–2636. doi: 10.1056/NEJMp058291. PubMed DOI

Fan X., Fan Z., Yang Z., Huang T., Tong Y., Yang D., Mao X., Yang M. Flavonoids—Natural Gifts to Promote Health and Longevity. Int. J. Mol. Sci. 2022;23:2176. doi: 10.3390/ijms23042176. PubMed DOI PMC

Xing W., Gao W., Zhao Z., Xu X., Bu H., Su H., Mao G., Chen J. Dietary Flavonoids Intake Contributes to Delay Biological Aging Process: Analysis from NHANES Dataset. J. Transl. Med. 2023;21:492. doi: 10.1186/s12967-023-04321-1. PubMed DOI PMC

Zhu S.Y., Jiang N., Tu J., Yang J., Zhou Y. Antioxidant and Anti-Aging Activities of Silybum Marianum Protein Hydrolysate in Mice Treated with D-Galactose. Biomed. Environ. Sci. 2017;30:623–631. doi: 10.3967/bes2017.083. PubMed DOI

Wellington K., Adis B.J. Silymarin: A Review of Its Clinical Properties in the Management of Hepatic Disorders. BioDrugs. 2001;15:465–489. doi: 10.2165/00063030-200115070-00005. PubMed DOI

Ramasamy K., Agarwal R. Multitargeted Therapy of Cancer by Silymarin. Cancer Lett. 2008;269:352–362. doi: 10.1016/j.canlet.2008.03.053. PubMed DOI PMC

Camini F.C., Costa D.C. Silymarin: Not Just Another Antioxidant. J. Basic Clin. Physiol. Pharmacol. 2020;31:20190206. doi: 10.1515/jbcpp-2019-0206. PubMed DOI

Adetuyi B.O., Omolabi F.K., Olajide P.A., Oloke J.K. Pharmacological, Biochemical and Therapeutic Potential of Milk Thistle (Silymarin): A Review. World News Nat. Sci. 2021;37:75–91.

Surai P.F. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants. 2015;4:204–247. doi: 10.3390/antiox4010204. PubMed DOI PMC

Haddadi R., Shahidi Z., Eyvari-Brooshghalan S. Silymarin and Neurodegenerative Diseases: Therapeutic Potential and Basic Molecular Mechanisms. Phytomedicine. 2020;79:153320. doi: 10.1016/j.phymed.2020.153320. PubMed DOI

Saller R., Meier R., Brignoli R. The Use of Silymarin in the Treatment of Liver Diseases. Drugs. 2001;61:2035–2063. doi: 10.2165/00003495-200161140-00003. PubMed DOI

Surai P.F., Surai A., Earle-Payne K. Silymarin and Inflammation: Food for Thoughts. Antioxidants. 2024;13:98. doi: 10.3390/antiox13010098. PubMed DOI PMC

Elangwe C.N., Morozkina S.N., Olekhnovich R.O., Polyakova V.O., Krasichkov A., Yablonskiy P.K., Uspenskaya M.V. Pullulan-Based Hydrogels in Wound Healing and Skin Tissue Engineering Applications: A Review. Int. J. Mol. Sci. 2023;24:4962. doi: 10.3390/ijms24054962. PubMed DOI PMC

Jabeen N., Sohail M., Shah S.A., Mahmood A., Khan S., ur Rehman Kashif M., Khaliq T. Silymarin Nanocrystals-Laden Chondroitin Sulphate-Based Thermoreversible Hydrogels; A Promising Approach for Bioavailability Enhancement. Int. J. Biol. Macromol. 2022;218:456–472. doi: 10.1016/j.ijbiomac.2022.07.114. PubMed DOI

D’souza A.A., Shegokar R. Polyethylene Glycol (PEG): A Versatile Polymer for Pharmaceutical Applications. Expert Opin. Drug Deliv. 2016;13:1257–1275. doi: 10.1080/17425247.2016.1182485. PubMed DOI

Shi L., Zhang J., Zhao M., Tang S., Cheng X., Zhang W., Li W., Liu X., Peng H., Wang Q. Effects of Polyethylene Glycol on the Surface of Nanoparticles for Targeted Drug Delivery. Nanoscale. 2021;13:10748–10764. doi: 10.1039/D1NR02065J. PubMed DOI

Chen B.M., Cheng T.L., Roffler S.R. Polyethylene Glycol Immunogenicity: Theoretical, Clinical, and Practical Aspects of Anti-Polyethylene Glycol Antibodies. ACS Nano. 2021;15:14022–14048. doi: 10.1021/acsnano.1c05922. PubMed DOI

Luís Â., Ramos A., Domingues F. Pullulan Films Containing Rockrose Essential Oil for Potential Food Packaging Applications. Antibiotics. 2020;9:681. doi: 10.3390/antibiotics9100681. PubMed DOI PMC

Sahu M., Reddy V.R.M., Kim B., Patro B., Park C., Kim W.K., Sharma P. Fabrication of Cu2ZnSnS4 Light Absorber Using a Cost-Effective Mechanochemical Method for Photovoltaic Applications. Materials. 2022;15:1708. doi: 10.3390/ma15051708. PubMed DOI PMC

Gurtner G.C., Callaghan M.J., Longaker M.T. Progress and Potential for Regenerative Medicine. Annu. Rev. Med. 2007;58:299–312. doi: 10.1146/annurev.med.58.082405.095329. PubMed DOI

Słota D., Florkiewicz W., Piętak K., Szwed A., Włodarczyk M., Siwińska M., Rudnicka K., Sobczak-Kupiec A. Preparation, Characterization, and Biocompatibility Assessment of Polymer-Ceramic Composites Loaded with Salvia Officinalis Extract. Materials. 2021;14:6000. doi: 10.3390/ma14206000. PubMed DOI PMC

Grigoras A.G. Drug Delivery Systems Using Pullulan, a Biocompatible Polysaccharide Produced by Fungal Fermentation of Starch. Environ. Chem. Lett. 2019;17:1209–1223. doi: 10.1007/s10311-019-00862-4. DOI

Atala A. Regenerative Medicine Strategies. J. Pediatr. Surg. 2012;47:17–28. doi: 10.1016/j.jpedsurg.2011.10.013. PubMed DOI

Singh R.S., Saini G.K. Advances in Industrial Biotechnology. Volume 8 IK International Publishing House Pvt. Ltd.; Delhi, India: 2016. Chapter 15 Pullulan as Th Erapeutic Tool in Biomedical Applications.

Xu M., Liu J., Sun J., Xu X., Hu Y., Liu B. Optical Microscopy and Electron Microscopy for the Morphological Evaluation of Tendons: A Mini Review. Orthop. Surg. 2020;12:366–371. doi: 10.1111/os.12637. PubMed DOI PMC