Synthesis and Characterization of Structural Properties of Cellulose-Based Polyurethane Structures for Controlled Methotrexate Release

Year 2023, , 2176 - 2184, 24.10.2023

Fatma Bilge Emre , Nilüfer Kıvılcım

https://doi.org/10.29130/dubited.1208589

Abstract

Within the scope of the study, cellulose-based polyurethane structures were developed to be used in the controlled and prolonged release of methotrexate (MTX), an important chemotherapeutic agent. A significant increase in survival rates has been recorded thanks to the targeted controlled release of drugs, the use of drugs and the improvement of supportive treatments. Methotrexate (MTX) is a drug that is frequently prescribed for the treatment of many cancer patients, such as acute lymphoblastic leukemia (ALL), and lymphoma, as well as many chronic diseases, such as rheumatoid arthritis and psoriasis. Polyethylene glycol-1000 (PEG-1000) structure was used to create the soft segment, especially among the cellulose-based polyurethane units, and the polyurethane (PU) structure with optimum swelling and drug loading properties was adjusted. The resulting PU structures were structurally characterized by Fourier Transfer Infrared Spectrophotometer (FTIR). The thermal stability and thermal properties of the structures were determined using Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC) devices. Surface properties and morphologies were determined by Scanning Electron Microscopy (SEM) using lyophilized hydrogel structures. The swelling properties and drug loading properties of the obtained polyurethane structures were investigated. The release kinetics were studied in detail by loading different ratios of MTX on the PEG-1000-based cellulose-based PU structure, which showed optimum properties. As a result, it was determined that the obtained cellulose-based PU structures had the appropriate structure and morphology for MTX loading and showed a long release time of approximately 24 hours.

Keywords

Cellulose, PU, Drug delivery system, Methotrexate (MTX), Hydrogel.

Kontrollü Metotreksat Salımı İçin Selüloz Temelli Poliüretan Yapıların Sentezi ve Yapısal Özelliklerinin Karakterizasyonu

Abstract

Çalışma kapsamında önemli bir kemoterapötik ajan olan metotreksatın (MTX) kontrollü ve uzun süreli salımında kullanılmak amacıyla selüloz temelli poliüretan yapıları geliştirildi. Hedefe yönelik kontrollü ilaç salımı ile ilaçların kullanımı ve destek tedavilerinin iyileştirilmesi sayesinde yaşam yüzdelerinde belirgin bir artış kaydedilmiştir. Metotreksat (MTX), akut lenfoblastik lösemi (ALL), lenfoma gibi pek çok kanser hastalarının tedavisinin yanı sıra romatoid artrit, psöriasis gibi pek çok kronik hastalıkların tedavisinde de sıklıkla reçete edilen bir ilaçtır. Özellikle selüloz temelli poliüretan üniteleri arasında yumuşak segmenti oluşturmak amacıyla Polietilen glikol-1000 (PEG-1000) yapısı kullanılarak optimum şişme ve ilaç yükleme özelliğine sahip poliüretan (PU) yapısı elde edildi. Elde edilen PU yapıları Fourier Transfer Infrared Spektrofotometresi (FTIR) ile yapısal olarak karakterize edildi. Yapıların termal kararlılıkları ve ısıl özellikleri Diferansiyel Termal Analiz (DTA) ve Diferansiyel Taramalı Kalorimetre (DSC) cihazları kullanılarak belirlendi. Yüzey özellikleri ve morfolojileri liyofilize edilmiş hidrojel yapılar kullanılarak Taramalı Elektron Mikroskopu (SEM) ile belirlendi. Elde edilen poliüretan yapılarının şişme özellikleri ve ilaç yükleme özellikleri incelendi. Optimum özellik gösteren PEG-1000 temelli selüloz bazlı PU yapısı üzerine farklı oranlarda MTX yüklemesi yapılarak salım kinetiği detaylı olarak çalışıldı. Sonuç olarak elde edilen selüloz temelli PU yapıları MTX yüklemesi için uygun yapı ve morfolojiye sahip olduğu ve yaklaşık olarak 24 saatlik uzun bir salım süresi gösterdiği belirlenmiştir.

Keywords

Selüloz, PU, İlaç salım sistemi, Metotreksat (MTX), Hidrojel

References

• [1] K.E. Uhrich, S.M. Cannizzaro, R.S. Langer, and K.M. Shakesheff, “Polymeric Systems for Controlled Drug Release,” Chem. Rev., vol. 99, pp. 3181−3198, 1999.
• [2] S. Senapati, A.K. Mahanta, S. Kumar, and P. Maiti, “Controlled drug delivery vehicles for cancer treatment and their performance,” Signal Transduction and Targeted Therapy, vol. 3, no. 1, pp. 1-19, 2018. 2183 [3] T.R. Hoare, and D.S. Kohane, “Hydrogels in drug delivery: Progress and challenges,” Polymer, vol. 49, no. 8, pp.1993-2007, 2008.
• [4] S. C Lee, I.K. Kwon, and K. Park, “Hydrogels for delivery of bioactive agents: A historical perspective,” Advanced Drug Delivery Reviews, vol. 65, no. 1, pp. 17-20, 2013.
• [5] W.E. Roorda, H.E. Bodde, A.G. De Boer, and H.E. Junginger, “Synthetic hydrogels as drug delivery systems,” Pharmaceutisch Weekblad, vol. 8, no. 3, pp. 165-189, 1986.
• [6] A. Srivastava, T. Yadav, S. Sharma, A. Nayak, A.A. Kumari, and N. Mishra, “Polymers in drug delivery,” Journal of Biosciences and Medicines, vol. 4, no. 1, pp. 69-84, 2015.
• [7] M. Dadsetan, Z. Liu, M. Pumberger, C.V. Giraldo, T. Ruesink, L. Lu, and M. J. Yaszemski, “A stimuli-responsive hydrogel for doxorubicin delivery,” Biomaterials, vol. 31, no. 31, pp. 8051-8062, 2015.
• [8] T.W. Steele, C.L. Huang, E. Widjaja, F.Y. Boey, J.S. Loo, and S.S. Venkatraman, “The effect of polyethylene glycol structure on paclitaxel drug release and mechanical properties of PLGA thin films,” Acta Biomaterialia, vol. 7, no. 5, pp. 1973-1983, 2011.
• [9] M. Casolaro, R. Cini, B. Del Bello, M. Ferrali, and E. Maellaro, “Cisplatin/hydrogel complex in cancer therapy,” Biomacromolecules, vol. 10, no. 4, pp. 944-949, 2009.
• [10] N. Taleblou, M. Sirousazar, Z.M. Hassan, and S.G. Khaligh, “Capecitabine-loaded anti-cancer nanocomposite hydrogel drug delivery systems: In vitro and in vivo efficacy against the 4T1 murine breast cancer cells,” Journal of Biomaterials Science, Polymer Edition, vol. 31, no. 1, pp. 72-92, 2020.
• [11] J. Blanchette, K. Park, and N.A. Peppas, “ Oral administration of chemotherapeutic agents using complexation hydrogels,” MRS Online Proceedings Library (OPL), 724, 2002.
• [12] N. Saba, P. Tahir, and M. Jawaid, “A review on potentiality of nano filler/natural fiber filled polymer hybrid composites,” Polymers, vol. 6, no. 8, pp. 2247-2273, 2014.
• [13] P. Albuquerque, L.C. Coelho, J.A. Teixeira, and M.G. Carneiro-da-Cunha, “Approaches in biotechnological applications of natural polymers,” Aims Molecular Science vol. 3, no. 3, pp. 386-425, 2016.
• [14] E. Ruel-Gariépy, M. Shive, A. Bichara, M. Berrada, D. Le Garrec, A. Chenite, and J.C. Leroux, “A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 57, no. 1, pp. 53-63, 2004.
• [15] S. Patel, and A. Goyal, “Applications of natural polymer gum arabic: a review,” International Journal of Food Properties, vol. 18, no. 5, pp. 986-998, 2015.
• [16] J.M. Anderson, and M.S. Shive, “Biodegradation and biocompatibility of PLA and PLGA microspheres,” Advanced Drug Delivery Reviews, vol. 28, no. 1, pp. 5-24, 1997.
• [17] S. Ghosh, “Recent research and development in synthetic polymer-based drug delivery systems,” Journal of Chemical Research, vol. 2004, no. 4, pp. 241-246, 2004.
• [18] E.S. Lee, S.W. Kim, S. H. Kim, J.R. Cardinal, and H. Jacobs, “Drug release from hydrogel devices with rate controlling barriers,” Journal of Membrane Science, vol. 7, no. 3, pp. 293-303, 1980.
• [19] A. Xie, M. Zhang, and S.I. Inoue, “Influence of β-cyclodextrin on morphologies and chemical, thermal, and mechanical properties of non-chain extended polyurethane elastomers,” Journal of Polymer Research, vol. 23, pp. 1-9, 2016.
• [20] Y. Zhou, H. Li, and Y.W. Yang, “Controlled drug delivery systems based on calixarenes,” Chinese Chemical Letters, vol. 26, no. 7, pp. 825-828, 2015.
• [21] F. Alışık, M. Burç, S. Titretir Duran, Ö. Güngör, M. A. Cengiz, S. Köytepe, “Development of Gum-Arabic-based polyurethane membrane-modified electrodes as voltammetric sensor for the detection of phenylalanine,” Polym. Bull. vol. 78, pp. 4699–4719, 2021.
• [22] L-J. Huang, L. Wen-Jau, and C. Yi-Chun, “Bio-Based Hydrogel and Aerogel Composites Prepared by Combining Cellulose Solutions and Waterborne Polyurethane,” Polymers vol. 14, no. 1: 204, 2022.
• [23] K.H. Ramteke, and L.K. Nath, “Formulation, evaluation and optimization of controlled release hydrogel microspheres for colon targeted drug delivery,” Journal of Pharmaceutical Sciences and Research, vol. 4, no. 2, pp. 1739, 2012.
• [24] M. Kamaci, “Polyurethane-based hydrogels for controlled drug delivery applications,” European Polymer Journal, vol. 123, 109444, 2020.
• [25] V. Gopinath, S. Saravanan, A.R. Al-Maleki, M. Ramesh, and J. Vadivelu, “A review of natural polysaccharides for drug delivery applications: Special focus on cellulose, starch and glycogen,” Biomedicine , and Pharmacotherapy, vol. 107, pp. 96-108, 2018.