Composite Cryogels for Drug Delivery Applications: A Preliminary Study with Dye as a Model Drug

Yıl 2023, Cilt: 6 Sayı: 1, 17 - 26, 30.04.2023

Didem Demir Karakuş Seda Ceylan Nimet Bölgen

https://doi.org/10.58692/jotcsb.1199436

Cited By: 1

Öz

Cryogels are suitable candidates to be used as drug release systems due to their interconnected pore structures, high surface areas, high liquid absorption capacities, and elasticity. With this purpose, we aimed to produce a cryogel structure to be used in drug release applications with the approach of tissue engineering. As biodegradable and biocompatible polymers chitosan and gelation were selected. The cryogels were fabricated using the combination of these polymers in the presence of glutaraldehyde under cryogenic conditions. The produced optimum gel scaffold was first characterized using FTIR, SEM, porosity, swelling ability, and degradation analyses. Successfully crosslinked gels exhibited an interconnected pore structure with an average pore diameter of 52.95 µm. As a result of the examination of the time-dependent weight change, it was also revealed that the cryogels have a liquid absorption capacity of about 500 times their dry weight and are biodegradable. The mainly characterized cryogel sample was evaluated for potential drug loading and release applications using methyl orange (MO) as a model drug. Gels, which swell in a short time, absorb the dye quickly and the cumulative release of the dye indicates that the gels are suitable for extended-release systems.

Anahtar Kelimeler

chitosan, gelatin, cryogel, drug delivery

Kaynakça

• Ak, F., Oztoprak, Z., Karakutuk, I., & Okay, O. (2013). Macroporous Silk Fibroin Cryogels. Biomacromolecules, 14(3), 719–727. https://doi.org/10.1021/bm3018033.
• Ayaz, F., Demir, D., & Bölgen, N. (2021). Differential anti-inflammatory properties of chitosan-based cryogel scaffolds depending on chitosan/gelatin ratio. Artificial Cells, Nanomedicine, and Biotechnology, 49(1), 682–690. https://doi.org/10.1080/21691401.2021.2012184.
• Bhasarkar, J., & Bal, D. (2019). Kinetic investigation of a controlled drug delivery system based on alginate scaffold with embedded voids. Journal of Applied Biomaterials & Functional Materials, 17(2), 228080001881746. https://doi.org/10.1177/2280800018817462.
• Bhat, S., Tripathi, A., & Kumar, A. (2011). Supermacroprous chitosan–agarose–gelatin cryogels: In vitro characterization and in vivo assessment for cartilage tissue engineering. Journal of The Royal Society Interface, 8(57), 540–554. https://doi.org/10.1098/rsif.2010.0455.
• Biondi, M., Ungaro, F., Quaglia, F., & Netti, P. A. (2008). Controlled drug delivery in tissue engineering. Advanced Drug Delivery Reviews, 60(2), 229–242. https://doi.org/10.1016/j.addr.2007.08.038.
• Demir, D., Ceylan, S., Göktürk, D., & Bölgen, N. (2021). Extraction of pectin from albedo of lemon peels for preparation of tissue engineering scaffolds. Polymer Bulletin, 78(4), 2211–2226. https://doi.org/10.1007/s00289-020-03208-1.
• Demir, D., Güreş, D., Tecim, T., Genç, R., & Bölgen, N. (2018). Magnetic nanoparticle-loaded electrospun poly(ε-caprolactone) nanofibers for drug delivery applications. Applied Nanoscience, 8(6), 1461–1469. https://doi.org/10.1007/s13204-018-0830-9.
• Demir, D., Öfkeli, F., Ceylan, S., & Bölgen, N. (2016). Extraction and Characterization of Chitin and Chitosan from Blue Crab and Synthesis of Chitosan Cryogel Scaffolds. Journal of the Turkish Chemical Society, Section A: Chemistry, 3(3). https://doi.org/10.18596/jotcsa.00634.
• Fernandes Queiroz, M., Melo, K., Sabry, D., Sassaki, G., & Rocha, H. (2014). Does the Use of Chitosan Contribute to Oxalate Kidney Stone Formation? Marine Drugs, 13(1), 141–158. https://doi.org/10.3390/md13010141.
• Ghanbarzadeh, B., & Almasi, H. (2013). Biodegradable Polymers. In R. Chamy (Ed.), Biodegradation—Life of Science. InTech. https://doi.org/10.5772/56230.
• Han, H. D., Song, C. K., Park, Y. S., Noh, K. H., Kim, J. H., Hwang, T., Kim, T. W., & Shin, B. C. (2008). A chitosan hydrogel-based cancer drug delivery system exhibits synergistic antitumor effects by combining with a vaccinia viral vaccine. International Journal of Pharmaceutics, 350(1–2), 27–34. https://doi.org/10.1016/j.ijpharm.2007.08.014.
• Hauck, M., Dittmann, J., Zeller-Plumhoff, B., Madurawala, R., Hellmold, D., Kubelt, C., Synowitz, M., Held-Feindt, J., Adelung, R., Wulfinghoff, S., & Schütt, F. (2022). Fabrication and Modelling of a Reservoir-Based Drug Delivery System for Customizable Release. Pharmaceutics, 14(4), 777. https://doi.org/10.3390/pharmaceutics14040777.
• Hezaveh, H., Muhamad, I. I., Noshadi, I., Shu Fen, L., & Ngadi, N. (2012). Swelling behaviour and controlled drug release from cross-linked κ-carrageenan/NaCMC hydrogel by diffusion mechanism. Journal of Microencapsulation, 29(4), 368–379. https://doi.org/10.3109/02652048.2011.651501.
• Kemençe, N., & Bölgen, N. (2017). Gelatin- and hydroxyapatite-based cryogels for bone tissue engineering: Synthesis, characterization, in vitro and in vivo biocompatibility: Gelatin and hydroxyapatite cryogels for bone tissue engineering. Journal of Tissue Engineering and Regenerative Medicine, 11(1), 20–33. https://doi.org/10.1002/term.1813.
• Khansari, S., Duzyer, S., Sinha-Ray, S., Hockenberger, A., Yarin, A. L., & Pourdeyhimi, B. (2013). Two-Stage Desorption-Controlled Release of Fluorescent Dye and Vitamin from Solution-Blown and Electrospun Nanofiber Mats Containing Porogens. Molecular Pharmaceutics, 10(12), 4509–4526. https://doi.org/10.1021/mp4003442.
• Kim, Y., Dalhaimer, P., Christian, D. A., & Discher, D. E. (2005). Polymeric worm micelles as nano-carriers for drug delivery. Nanotechnology, 16(7), S484–S491. https://doi.org/10.1088/0957-4484/16/7/024.
• Li, J., Wang, Y., Zhang, L., Xu, Z., Dai, H., & Wu, W. (2019). Nanocellulose/Gelatin Composite Cryogels for Controlled Drug Release. ACS Sustainable Chemistry & Engineering, 7(6), 6381–6389. https://doi.org/10.1021/acssuschemeng.9b00161.
• Loc, N. X., Tuyen, P. T. T., Mai, L. C., & Phuong, D. T. M. (2022). Chitosan-Modified Biochar and Unmodified Biochar for Methyl Orange: Adsorption Characteristics and Mechanism Exploration. Toxics, 10(9), 500. https://doi.org/10.3390/toxics10090500.
• Lu, Z., Yeh, T.-K., Tsai, M., Au, J. L.-S., & Wientjes, M. G. (2004). Paclitaxel-Loaded Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy. Clinical Cancer Research, 10(22), 7677–7684. https://doi.org/10.1158/1078-0432.CCR-04-1443.
• Martins, J. P., Ferreira, M. P. A., Ezazi, N. Z., Hirvonen, J. T., Santos, H. A., Thrivikraman, G., França, C. M., Athirasala, A., Tahayeri, A., & Bertassoni, L. E. (2018). 3D printing: Prospects and challenges. In Nanotechnologies in Preventive and Regenerative Medicine (pp. 299–379). Elsevier. https://doi.org/10.1016/B978-0-323-48063-5.00004-6.
• Meena, L. K., Raval, P., Kedaria, D., & Vasita, R. (2018). Study of locust bean gum reinforced cyst-chitosan and oxidized dextran based semi-IPN cryogel dressing for hemostatic application. Bioactive Materials, 3(3), 370–384. https://doi.org/10.1016/j.bioactmat.2017.11.005.
• Mondal, D., Griffith, M., & Venkatraman, S. S. (2016). Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges. International Journal of Polymeric Materials and Polymeric Biomaterials, 65(5), 255–265. https://doi.org/10.1080/00914037.2015.1103241.
• Nagahama, H., Maeda, H., Kashiki, T., Jayakumar, R., Furuike, T., & Tamura, H. (2009). Preparation and characterization of novel chitosan/gelatin membranes using chitosan hydrogel. Carbohydrate Polymers, 76(2), 255–260. https://doi.org/10.1016/j.carbpol.2008.10.015.
• Pancholi, K., Stride, E., & Edirisinghe, M. (2009). In Vitro Method to Characterize Diffusion of Dye from Polymeric Particles: A Model for Drug Release. Langmuir, 25(17), 10007–10013. https://doi.org/10.1021/la900694k.
• Piazzini, V., Landucci, E., D’Ambrosio, M., Tiozzo Fasiolo, L., Cinci, L., Colombo, G., Pellegrini-Giampietro, D. E., Bilia, A. R., Luceri, C., & Bergonzi, M. C. (2019). Chitosan coated human serum albumin nanoparticles: A promising strategy for nose-to-brain drug delivery. International Journal of Biological Macromolecules, 129, 267–280. https://doi.org/10.1016/j.ijbiomac.2019.02.005.
• Pradini, D., Juwono, H., Madurani, K. A., & Kurniawan, F. (2018). A preliminary study of identification halal gelatin using quartz crystal microbalance (QCM) sensor. Malaysian Journal of Fundamental and Applied Sciences, 14(3), 325–330.
• Qian, Y.-F., Zhang, K.-H., Chen, F., Ke, Q.-F., & Mo, X.-M. (2011). Cross-Linking of Gelatin and Chitosan Complex Nanofibers for Tissue-Engineering Scaffolds. Journal of Biomaterials Science, Polymer Edition, 22(8), 1099–1113. https://doi.org/10.1163/092050610X499447.
• Rogers, Z. J., & Bencherif, S. A. (2019). Cryogelation and Cryogels. Gels, 5(4), 46. https://doi.org/10.3390/gels5040046.
• Şarkaya, K., & Allı, A. (2021). Synthesis and characterization of cryogels of p(HEMA-N-vinylformamide) and p(HEMA-N-Vinylpyrrolidone) for chemical release behaviour. Journal of Porous Materials, 28(3), 853–865. https://doi.org/10.1007/s10934-021-01037-9.
• Shera, S. S., Sahu, S., & Banik, R. M. (2018). Preparation of Drug Eluting Natural Composite Scaffold Using Response Surface Methodology and Artificial Neural Network Approach. Tissue Engineering and Regenerative Medicine, 15(2), 131–143. https://doi.org/10.1007/s13770-017-0100-z.
• Singh, D., Tripathi, A., Nayak, V., & Kumar, A. (2011). Proliferation of Chondrocytes on a 3-D Modelled Macroporous Poly(Hydroxyethyl Methacrylate)–Gelatin Cryogel. Journal of Biomaterials Science, Polymer Edition, 22(13), 1733–1751. https://doi.org/10.1163/092050610X522486.
• Surya, R., Mullassery, M. D., Fernandez, N. B., Thomas, D., & Jayaram, P. S. (2020). Synthesis and characterization of a pH responsive and mucoadhesive drug delivery system for the controlled release application of anti-cancerous drug. Arabian Journal of Chemistry, 13(5), 5262–5276. https://doi.org/10.1016/j.arabjc.2020.03.005.
• Vo, T. S., Vo, T. T. B. C., Nguyen, T. S., & Ti̇En, T. T. (2021). Fabrication and Characterization of Gelatin/Chitosan Hydrogel Utilizing as Membranes. Journal of the Turkish Chemical Society Section A: Chemistry, 1045–1056. https://doi.org/10.18596/jotcsa.942478.
• Wang, J., Wang, G., Shan, H., Wang, X., Wang, C., Zhuang, X., Ding, J., & Chen, X. (2019). Gradiently degraded electrospun polyester scaffolds with cytostatic for urothelial carcinoma therapy. Biomaterials Science, 7(3), 963–974. https://doi.org/10.1039/C8BM01317A.
• Yao, J., Wang, Y., Ma, W., Dong, W., Zhang, M., & Sun, D. (2019). Dual-Drug-Loaded Silk Fibroin/PLGA Scaffolds for Potential Bone Regeneration Applications. Journal of Nanomaterials, 2019, 1–16. https://doi.org/10.1155/2019/8050413.
• Yusop, A. H., Sarian, M. N., Januddi, F. S., Ahmed, Q. U., Kadir, M. R., Hartanto, D., Hermawan, H., & Nur, H. (2018). Structure, degradation, drug release and mechanical properties relationships of iron-based drug eluting scaffolds: The effects of PLGA. Materials & Design, 160, 203–217. https://doi.org/10.1016/j.matdes.2018.09.019.