Physicochemical Characterization and Network Modeling of Cross-Linked Inulin Based Hydrogels

Abstract

Inulin (In)-based hydrogels were produced using 1,3-diepoxybutane (BDE) as a crosslinker under basic conditions. The amount of BDE influences the network properties of In/BDE gels. FTIR spectroscopy revealed the formation of ether bridges, indicating successful synthesis of gels, and thermal characterization confirmed that higher cross-linking density increased polymeric matrix stability. In PBS medium, the equilibrium swelling capacity decreased from 3.32 g/g to 1.44 g/g with increasing BDE content. Flory–Rehner thermodynamic analysis indicated that restricted swelling was driven by an 18-fold increase in effective crosslink density (𝜈𝑒) and reduction in the molecular weight between crosslinks (𝑀𝑐̅̅̅̅) 1023.89 to 57.14 gmol-1. Kinetic data followed Fickian diffusion with exponent (n) values between 0.126 and 0.305, fitting the Pseudo-Second Order (PSO) model well. Overall structural evidence indicates that the developed In/BDE hydrogel matrices possess finely adjustable configurations. This architectural control makes them excellent candidates for both controlled-release therapeutics and wastewater purification applications.

Keywords

• Inulin
• Hydrogel
• Swelling
• Fickian diffusion
• Cross-linking.

References

1. [1]. El-Husseiny, H, M, Mady, E, A, Hamabe, L, Abugomaa, A, Shimada, K, Yoshida, T, Tanaka, T, Yokoi, A, Elbadawy, M, Tanaka, R. 2022. Smart/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications. Materials Today Bio; 13:100186.
2. [2]. Lu, P, Ruan, D, Huang, M, Tian, M, Zhu, K, Gan, Z, Xiao, Z. 2024. Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions. Signal Transduction and Targeted Therapy; 9(1):166.
3. [3]. Prakash, A, Malviya, R, Sridhar, S, B, Wadhwa, T, Shareef, J, Tripathy, D, B. 2025. Polysaccharides as functional biomaterials in 3D bioprinting: Strategies for antimicrobial applications. Next Materials; 9:101255.
4. [4]. Arif, Z, U. 2025. The role of polysaccharide-based biodegradable soft polymers in the healthcare sector. Advanced Industrial and Engineering Polymer Research; 8(1):132-156.
5. [5]. Karimi, I, Ghowsi, M, Mohammed, L, J, Haidari, Z, Nazari, K, Schiöth, H, B. 2025. Inulin as a Biopolymer; Chemical Structure, Anticancer Effects, Nutraceutical Potential and Industrial Applications: A Comprehensive Review. Polymers; 17(3): 412.
6. [6]. Del Olmo, J, Pérez-álvarez, L, Martínez, S, Cid, B, González, R, P, Vilas-Vilela, J, L, Alonso, J, M. 2022. Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications Gels; 8(4):223.
7. [7]. Della Sala, F, di Gennaro, M, Makvandi, P, Borzacchiello, A. 2024. A Covalently Cross-Linked Hyaluronic Acid/Carboxymethyl Cellulose Composite Hydrogel as a Potential Filler for Soft Tissue Augmentation. Gels; 10(1):67.
8. [8]. Xue, Y, Chen, H, Xu, C, Yu, D, Xu, H, Hu, Y. 2020. Synthesis of hyaluronic acid hydrogels by crosslinking the mixture of high-molecular-weight hyaluronic acid and low-molecular-weight hyaluronic acid with 1,4-butanediol diglycidyl ether. RSC Advances; 10(12):7206–7213.

9. [9]. Bashir, S, Hina, M, Iqbal, J, Rajpar, H., Mujtaba, A, Alghamdi, A, Wageh, S, Ramesh, K, Ramesh, S. 2020. Fundamental concepts of hydrogels: Synthesis, properties, and their applications. Polymers; 12(11):1-60.
10. [10]. Roca-Arroyo, F, Gutierrez-Rivera, A., Morton, D, Castilla-Casadiego, A. 2025. Hydrogel Network Architecture Design Space: Impact on Mechanical and Viscoelastic Properties. Gels; 11(8):588.
11. [11]. Sepe, F, Valentino, A, Marcolongo, L, Petillo, O, Calarco, A, Margarucci, S, Peluso, G, Conte, R. 2025. Polysaccharide Hydrogels as Delivery Platforms for Natural Bioactive Molecules: From Tissue Regeneration to Infection Control. Gels;11(3):198.
12. [12]. Camponeschi, F, Atrei, A, Rocchigiani, G, Mencuccini, L, Uva, M, Barbucci, R. 2015. New formulations of polysaccharide-based hydrogels for drug release and tissue engineering. Gels;1(1):3-23.
13. [13]. Wang, R, Cheng, C, Wang, H, Wang, D. 2024. Swollen hydrogel nanotechnology: Advanced applications of the rudimentary swelling properties of hydrogels. ChemPhysMater; 3(4): 357-375.
14. [14]. Peters, J. T, Wechsler, E., Peppas, A. 2021. Advanced biomedical hydrogels: Molecular architecture and its impact on medical applications. Regenerative Biomaterials; 8(6).
15. [15]. Afinjuomo, F, Barclay, G, Song, Y, Parikh, A, Petrovsky, N, Garg, S. 2019. Synthesis and characterization of a novel inulin hydrogel crosslinked with pyromellitic dianhydride. Reactive and Functional Polymers; 134: 104–111.
16. [16]. Akgun, S, Bostan, S, Un, I, Sadak, A, E, Bahadori, F, Eroglu, S. 2025. Physico-chemical and spectroscopic characterization of hyaluronic acid hydrogels crosslinked with 1,4-butanediol diglycidyl ether (BDDE). International Journal of Biological Macromolecules; 308:142050.
17. [17]. Eyigor, A, Bahadori, F, Yenigun, B, Eroglu, S. 2018. Beta-Glucan based temperature responsive hydrogels for 5-ASA delivery. Carbohydrate Polymers; 201:454–463.
18. [18]. Ahmed, L, Atif, R, Salah Eldeen, T, Yahya, I, Omara, A, Eltayeb, M. 2019. Study the Using of Nanoparticles as Drug Delivery System Based on Mathematical Models for Controlled Release. International Journal of Latest Technology in Engineering; 8(5):52-56.
19. [19]. Hendy, M, Mansour, S, Abdel-Megeed, A, Al-Oufy, A, Salem, M. 2025. Swelling Properties of Superabsorbent Hydrogels Based on Carboxymethyl Cellulose With Silica, Kaolin, and Bentonite Particles for Agricultural Applications. ChemistrySelect; 10(45): e04489
20. [20]. Wu, C, Tseng, L, Huang, C, Juang, S. 2009. Characteristics of pseudo-second-order kinetic model for liquid-phase adsorption: A mini-review. Chemical Engineering Journal;151(1-3):1-9.
21. [21]. Bullen, C, Saleesongsom, S, Gallagher, K, Weiss, J. 2021. A Revised Pseudo-Second-Order Kinetic Model for Adsorption, Sensitive to Changes in Adsorbate and Adsorbent Concentrations. Langmuir; 37(10): 3189–3201.
22. [22]. Plazinski, W, Dziuba, J, Rudzinski, W. 2013. Modeling of sorption kinetics: The pseudo-second order equation and the sorbate intraparticle diffusivity. Adsorption;19(5):1055–1064.
23. [23]. Chikkerur, J, Samanta, K, Kolte, P, Dhali, A, Roy, S. 2020. Production of Short Chain Fructo-oligosaccharides from Inulin of Chicory Root Using Fungal Endoinulinase. Applied Biochemistry and Biotechnology; 191(2):695–715.
24. [24]. Chehardoli, G, Norouzian, P, Firozian, F. 2020. Inulin-Grafted Stearate (In-g-St) as the Effective Self-Assembling Polymeric Micelle: Synthesis and Evaluation for the Delivery of Betamethasone. Journal of Nanomaterials; 1:6579538.
25. [25]. Molina, A, Elizalde-Mata, A, Hernández-Martínez, R, Fonseca, G, Soto, C, Rodríguez-Morales, L, Estevez, M. 2020. Synthesis and characterization of inulin-based responsive polyurethanes for breast cancer applications. Polymers; 12(4):865.
26. [26]. Rasjava, il, Kurniati, F, Hertadi, R. 2025. Engineered acetylated inulin nanoparticles for enhanced oral insulin delivery: sustained release, structural stability, and in vivo efficacy. RSC Advances; 15(32): 26216–26228.
27. [27]. Baig, T, Abdel-Azeim, S, Ganie, A, Warsame, M, Mady, F. 2025. Phosphonated Inulin as an Eco-Friendly Thermally Stable Scale Inhibitor for the Oil and Gas Industry: Synthesis, Characterization, Efficacy, and Molecular Insights. ACS Sustainable Chemistry and Engineering; 13(4):1762–1774.
28. [28]. Lv, K, Shen, H, Sun, J, Huang, X, Du, H. 2024. Acylated Inulin as a Potential Shale Hydration Inhibitor in Water Based Drilling Fluids for Wellbore Stabilization. Molecules;29(7):1456.
29. [29]. Abdel-Hamid, S, Hamouda, F, Abd El-Aal, H, Badawy, A. 2022. Distinctive Application of the Consortium of Chlorella vulgaris and Anabaena oryzae Toward Different Planting Dates and Climate Change on Jerusalem Artichoke Yield. Journal of Plant Growth Regulation; 41(2):479–493.
30. [30]. Vargas-Osorio, Z, González Castillo, I, Mutlu, N, Vidomanová, E, Michálek, M, Galusek, D, Boccaccini, R. 2024. Tailorable mechanical and degradation properties of KCl-reticulated and BDDE-crosslinked PCL/chitosan/κ-carrageenan electrospun fibers for biomedical applications: Effect of the crosslinking-reticulation synergy. International Journal of Biological Macromolecules; 265:130647.
31. [31]. Li, P, Wang, T, He, J, Jiang, J, Lei, F. 2021. Diffusion of water and protein drug in 1,4-butanediol diglycidyl ether crosslinked galactomannan hydrogels and its correlation with the physicochemical properties. International Journal of Biological Macromolecules; 183:1987–2000.
32. [32]. Al-Sibani, M, Al-Harrasi, A, Neubert, R. 2018. Characterization of Linear and Chemically Cross-linked Hyaluronic acid using Various Analytical Techniques Including FTIR, ESI-MS, H1 NMR, and SEM. Journal of Biochemistry and Analytical Studies; 3(1):1-8.
33. [33]. Djordjević, M, Ambrus, R, Maravić, N, Vidović, S, Šoronja-Simović, D, Petrović, J, Šereš, Z. 2022. Impact of Short-Time Micronization on Structural and Thermal Properties of Sugar Beet Fibre and Inulin. Food Technology and Biotechnology; 60(4):543–555.
34. [34]. Liu, Z, Basem, A, Mostafa, L, Jasim, J, Al-Rubaye, H, Salahshour, S, Hekmatifar, M, Esmaeili, S. 2024. Investigating the effect of pH on the swelling process, mechanical and thermal attributes of polyacrylamide hydrogel structure: A molecular dynamics study. Case Studies in Thermal Engineering; 55:104148.
35. [35]. Bang, S, Das, D, Yu, J, Noh, I. 2017. Evaluation of MC3T3 cells proliferation and drug release study from sodium hyaluronate-1,4-butanediol diglycidyl ether patterned gel. Nanomaterials; 7(10):328.
36. [36]. Shakor, M, Tayib, M, AbdulRazak, A, Shnain, Y, Al-Shafei, E. 2025. Thermogravimetric Analysis Integrated with Mathematical Methods and Artificial Neural Networks for Optimal Kinetic Modeling of Biomass Pyrolysis: A Review. ACS Omega; 10:36750-36770.
37. [37]. Felix, B, Chen, H, Ubando, T, Park, K, Lin, A, Pugazhendhi, A, Nguyen, B, Dong, D. 2022. A comprehensive review of thermogravimetric analysis in lignocellulosic and algal biomass gasification. Chemical Engineering Journal; 445:136730.
38. [38]. Xie, G, Lu, Y, Lu, X, Zhang, Z, Lin, S. 2025. Measurement Error Analysis and Thermal Degradation Kinetic Model Improvement for Thermogravimetric Analyzers. Polymers;17(17):2390.
39. [39]. Molina, A, Elizalde-Mata, A, Hernández-Martínez, R, Fonseca, G, Soto, C, Rodríguez-Morales, L, Estevez, M. 2020. Synthesis and characterization of inulin-based responsive polyurethanes for breast cancer applications. Polymers; 12(4):865.
40. [40]. Alves, M, Quevedo, V, de Rezende Duek, A, Komatsu, D. 2026. Epoxidized natural rubber with hyaluronic acid blend for potential biomaterial application. Polymer Bulletin; 83(1):1-14.
41. [41]. Akgun, S, Bostan, M, Un, I, Sadak, E, Bahadori, F, Eroglu, S. 2025. Physico-chemical and spectroscopic characterization of hyaluronic acid hydrogels crosslinked with 1,4-butanediol diglycidyl ether (BDDE). International Journal of Biological Macromolecules, 308:142050.
42. [42]. Zawadzka, O, Gnatowski, P, Piłat, E, Kucińska-Lipka, J. 2025. Investigation on the swelling kinetics of gelatin based hydrogels. Chemistry and Chemical Technology;19(2):259–269.
43. [43]. Lee, Y, Cheon, C, Son, S, Kim, Z, Kim, T, Jang, W, Kim, S. 2015. Influence of molecular weight on swelling and elastic modulus of hyaluronic acid dermal fillers. Polymer (Korea); 39(6):976–980.
44. [44]. Carbinatto, M, de Castro, D, Evangelista, C, Cury, F. 2014. Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices. Asian Journal of Pharmaceutical Sciences; 9(1): 27–34.
45. [45]. Richbourg, R, Peppas, A. 2020. The swollen polymer network hypothesis: Quantitative models of hydrogel swelling, stiffness, and solute transport. Progress in Polymer Science; 105:101243.
46. [46]. Klančar, U, Horvat, M, Baumgartner, S. 2012. Correlating cellulose derivative intrinsic viscosity with mechanical susceptibility of swollen hydrophilic matrix tablets. AAPS PharmSciTech;13(3), 903–910.
47. [47]. Arayesh, S, Tanhaei, B, Khoshkho, M, Shahrak, N, Ayati, A, Far, K. 2025. Enhanced dual-drug loaded κ-carrageenan/agar hydrogel films for wound dressing: Optimizing swelling and drug release. International Journal of Biological Macromolecules; 306:141295.
48. [48]. Jayanudin, R, Meliana, Y, Pitaloka, B, Lestari, D, Barleany, R, Yulvianti, M, Kanani, N, Prasetyo, D. 2026. Swelling Kinetics and Saponification-Assisted Synthesis of Chitosan-g-PAA Superabsorbent Hydrogels. Chemical Engineering and Technology; 49(3): e70186.
49. [49]. Karakuş, R, Türk, S, Guney, E, G, Syzdykbayev, M, Appazov, O, Özacar, M. 2024. Investigation of Tannic Acid Crosslinked PVA/PEI-Based Hydrogels as Potential Wound Dressings with Self-Healing and High Antibacterial Properties. Gels;10(11):682.
50. [50]. Li, X, Wang, Y, Li, A, Ye, Y, Peng, S, Deng, M, Jiang, B. 2019. A novel pH- And salt-responsive n-succinyl-chitosan hydrogel via a one-step hydrothermal process. Molecules;24(23):4211.
51. [51]. Kim, Y, Park, W, Lee, Y, Seo, H. 2020. Correlation between the crosslink characteristics and mechanical properties of natural rubber compound via accelerators and reinforcement. Polymers; 12(9):1–14.
52. [52]. Hoti, G, Caldera, F, Cecone, C, Pedrazzo, R, Anceschi, A, Appleton, L, Monfared, K, Trotta, F. 2021. Effect of the cross-linking density on the swelling and rheological behavior of ester-bridged β-cyclodextrin nanosponges. Materials; 14(3): 1–20.
53. [53]. Xia, Z, Patchan, M, Maranchi, J, Elisseeff, J, Trexler, M. 2013. Determination of crosslinking density of hydrogels prepared from microcrystalline cellulose. Journal of Applied Polymer Science; 127(6): 4537–4541.
54. [54]. Borges, P, Papavasiliou, G, Teymour, F. 2023. Characterizing the Molecular Architecture of Hydrogels and Crosslinked Polymer Networks beyond Flory-Rehner. II: Experiments. Biomacromolecules; 24(4): 1585–1603.