Development of a Controlled Released System Based on IPN Types Hydrogel for Cartilage Repair

Year 2024, Volume: 37 Issue: 2, 576 - 591, 01.06.2024

Evrim Sever , Mehlika Pulat

https://doi.org/10.35378/gujs.1295326

Abstract

The purpose of this study is to develop a controlled Fluconazole and Naproxen releasing system for cartilage repair. Interpenetrating polymer network (IPN) type of hydrogels were prepared by using different ratios of 2-Hydroxyethyl methacrylate (HEMA) and gelatin. The hydrogels were synthesized by using ammonium persulfate (APS) and sodium metabisulfite (SBS) as initiator pair and ethylene glycol dimethacrylate (EGDMA) and glutaraldehyde (GA) as cross linkers. The prepared hydrogels were characterized via hydrogel formation and swelling/degradation measurements, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscope (SEM) analysis. From swelling tests, it is observed that semi-IPN hydrogels swell much more than full-IPNs which crosslinked by two agents, EGDMA and GA. The higher ratios of HEMA/gelatin negatively affect swelling values. In general, the IPN hydrogel discs were not affected by the variation of temperature. The release studies of Fluconazole and Naproxen were performed at 37 ⁰C and it is found that the swelling and releasing profiles were similar to each other. The releases of drugs increase rapidly at first and then complies nearly 36 h-48 h. Because of the looser and porous structure, semi-IPN hydrogels have higher release values than full-IPNs.

Keywords

Hydrogel, Gelatin, Cartilage, 2-Hydroxyethyl methacrylate, Controlled drug release

Supporting Institution

Gazi Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Project Number

FDK-6920

Thanks

The financial and technical support of the research from Gazi University Scientific Research Projects Unit (Project Code: FDK-2021-6920).

References

• [1] Elisseeff, J., Anseth, K., Sims, D., McIntosh, W., Randolph, M., and Langer, R., “Transdermal photopolymerization for minimally invasive implantation”, The Proceedings of the National Academy of Sciences, 96(6), 3104-3107, (1999).
• [2] Pulat, M., Özgündüz, H. İ., “Swelling behavior and morphological properties of semi-IPN hydrogels based on ionic and non-ionic components”, Bio-Medical Materials and Engineering, 24(4): 1725-1733, (2014).
• [3] Lin, C.C., Metters, A.T., “Hydrogels in controlled release formulations: network design and mathematical modeling”, Advanced Drug Delivery Reviews, 58(12-13): 1379-1408, (2006).
• [4] Slaughter, B.V., Khurshid, S.S., Fisher, O.Z., Khademhosseini, A., and Peppas, N.A., “Hydrogels in regenerative medicine”, Advanced Materials, 21: 3307-3329, (2009).
• [5] Pedley, D.G., Skelly, P.J., and Tighe, B.J., “Hydrogels in biomedical applications”, British Polymer Journal, 12(3): 99-110, (1980).
• [6] Refojo, M., Yasuda, H., “Hydrogels from 2‐hydroxyethyl methacrylate and propylene glycol monoacrylate”, Journal of Applied Polymer Science, 9: 2425-2435, (1965).
• [7] Hejcl, A., Lesný, P., Prádný, M., Sedý, J., Zámecník, J., Jendelová, P., Michálek, J., and Syková, E., “Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair”, Journal of Materials Science: Materials in Medicine, 20: 1571-1577, (2009).
• [8] Saini, R., Bajpai, J., and Bajpai, A.K., “Synthesis of poly (2-hydroxyethyl methacrylate) (PHEMA) based nanoparticles for biomedical and pharmaceutical applications”, Methods in Molecular Biology, 906: 321-328, (2012).
• [9] Ye, J., Yang, G., Zhang, J., Xiao, Z., He, L., Zhang, H., and Liu, Q., “Preparation and characterization of gelatin-polysaccharide composite hydrogels for tissue engineering”, PeerJ, 11022, (2021).
• [10] Rosellini, E., Lazzeri, L., Maltinti, S., Vanni, F., Barbani, N., and Cascone, M.G., “Development and characterization of a suturable biomimetic patch for cardiac applications”, Journal of Materials Science: Materials in Medicine, 30: Article Number 126, (2019).
• [11] Vukovi´c, J.S., Filipovi´c, V.V., Babi´c Radi´c M.M., Vukomanovi´c, M., Milivojevic D., Ilic-Tomic, T., Nikodinovic-Runic, J., and Tomi´c, S.Lj. “In Vitro and In Vivo Biocompatible and Controlled Resveratrol Release Performances of HEMA/Alginate and HEMA/Gelatin IPN Hydrogel Scaffolds”, Polymers, 14: 4459, (2022). [12] Babi´c Radi´c M.M., Filipovi´c, V.V., Vukomanovi´c, M., Runi´c Y.N., and Tomi´c, S.Lj. “Degradable 2-Hydroxyethyl Methacrylate/Gelatin/Alginate Hydrogels Infused by Nanocolloidal Graphene Oxide as Promising Drug Delivery and Scaffolding Biomaterials1, Gels, 8(1): 22, (2022).
• [13] Jaiswal, M., Koul, V. “Assessment of multicomponent hydrogel scaffolds of poly(acrylic acid-2-hydroxy ethyl methacrylate)/gelatin for tissue engineering applications”, Journal of Biomaterials Applications, 27 (7): 848-861, (2013).
• [14] Abramoff, B., Caldera, F.E., “Osteoarthritis: pathology, diagnosis, and treatment options”, Medical Clinics of North America,104: 293-311, (2020).
• [15] Sha’ban, M., Radzi, M.A.A., “Scaffolds for cartilage regeneration: to use or not to use”, Advances in Experimental Medicine and Biology, 1249: 97-114, (2020).
• [16] Fox, A.J.S., Bedi, A., and Rodeo, S.A., “The basic science of articular cartilage: structure, composition, and function”, Sports Health, 1(6): 461-468, (2009).
• [17] Goldring, M.B., Marcu, K.B., “Cartilage homeostasis in helath and rheumatic diseases”, Arthritis Research and Therapy, 11: Article Number 224, (2009).
• [18] Looij, S.M., Jong, O.G., Vermonden, T., and Lorenowicz, M. J., “Injectable hydrogels for sustained delivery of extracellular vesicles in cartilage regeneration”, Journal of Controlled Release, 355: 685-708, (2023).
• [19] Bennett, J., Dolin, R., and Blaser, M. J., “Mandell, Douglas, and Bennett's Principles and Practice of Infectious Disease”, 7. United States: Elsevier, (2019).
• [20] Ruderman, E.M., Flaherty, J.P., “Fungal Infections of Bones and Joints. Kelley and Firestein's Textbook of Rheumatology”, 11. Philadelphia: Elsevier, Chapter 119: 1918-1928, (2021).
• [21] Pasko, M.T., Piscitelli, S.C., and Van Slooten, A.D., “Fluconazole: a new triazole antifungal agent. Annals of Pharmacotherapy”, The Dalian Institute of Chemical Physics, 24: 860-867, (1990).
• [22] Parolini, M., “Toxicity of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: A review”, Science of the Total Environment, 740: 140043, (2020).
• [23] Pulat, M., Asıl, D.,” Fluconazole release through semi-interpenetrating polymer network hydrogels based on chitosan, acrylic acid, and citraconic acid”, Journal of Applied Polymer Science, 113: 2613–2619, (2009).
• [24] Song, S.Z., Cardinal, J.R., Kim, S.H., and Kim, S.W., “Progestin Permeation Through Polymer Membranes V: Progesterone Release from Monolithic Hydrogel Devices”, Journal of Pharmaceutical Sciences, 70 (2): 216-219, (1981).
• [25] Pal, A., Bajpai, J., and Bajpai, A.K., “Easy fabrication and characterization of gelatin nanocarriers and in vitro investigation of swelling controlled release dynamics of paclitaxel”, Polymer Bulletin, 75: 4691–4711, (2018).
• [26] Bartyzel, A., “Synthesis, thermal study and some properties of N2O4—donor Schiff base and its Mn (III), Co (II), Ni (II), Cu (II) and Zn (II) complexes”, Journal of Thermal Analysis and Calorimetry, 127: 2133-2147, (2017).
• [27] Ramaraj, B., Radhakrishnan, G., “Modification of the dynamic swelling behavior of poly (2-hydroxyethyl methacrylate) hydrogels in water through interpenetrating polymer network (IPNs)”, Polymer, 35: 2167–2173, (1994).
• [28] Johlin, J.M., “The Isoelectric Point of Gelatin and Its Relation to the Minimum Physical Properties of Gelatin”, Journal of Biological Chemistry, 86 (1): 231-243, (1930).
• [29] Siangsanoh, C., Ummartyotin, S., Sathirakul, K., Rojanapanthu, P., and Treesuppharat, W., “Fabrication and characterization of triple-responsive composite hydrogel for targeted and controlled drug delivery system”, Journal of Molecular Liquids, 256: 90-99, (2018).
• [30] Xing, Q., Yates, K., Vogt, C., Qian, Z., Frost, M.C., and Zhao, F., “Increasing Mechanical Strength of Gelatin Hydrogels by Divalent Metal Ion Removal”, Scientific Reports, 4: Article Number: 4706, (2014).
• [31] Schiave, L. A., Nascimento, E., Vilar, F. C., Haes, T. M., Takayanagui, O. M., Gaitani, C. M., and Martinez, R., “Fluconazole levels in serum and cerebrospinal fluid according to daily dosage in patients with cryptococcosis and other fungal infections”, Brazilian Journal of Infectious Diseases, 22 (1): 11-15, (2018).
• [32] Buijk, S.L.C.E., Gyssens, I.C., Mouton, J.W., Verbrugh, H.A., Touw, D.J. and Bruining, H.A., “Pharmacokinetics of sequential intravenous and enteral fluconazole in critically ill surgical patients with invasive mycoses and compromised gastro-intestinal function”, Intensive Care Medicine, 27: 115-121, (2001).
• [33] Paulus, H.E., Furst, D.E., and Dromgoole, S.H., “Drugs for Rheumatic Disease”, Churchill Livingstone, (1987).
• [34] Ritger, P.L., Peppas, N.A., “A simple equation for description of solute release I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs”, Journal of Controlled Release, 5(1): 23-36, (1987).
• [35] Cooper, S., Horbett, T., Ratner, M., and Stayton, P. “Gels, Genes, Grafts and Giants”, Festschrift on the Occasion of the 70th Birthday of Allan S. Hoffman. CRC Press, p36, (2005).
• [36] Işık, B. “Swelling behavior of acrylamide-2-Hydroxyethyl methacrylate hydrogels”, Turkish Journal of Chemistry, 24: 147-156, (2000).