Swelling and Anticancer Drug Uptake Capacity of Chitosan/Hyaluronic Acid/Gelatin Hydrogels

Yıl 2024, , 21 - 26, 31.07.2024

Betül Taşdelen , Ömer Faruk Güder

https://doi.org/10.55581/ejeas.1447096

Öz

Nowadays, the number of patients diagnosed with cancer is increasing day by day. Chemotherapy is an indispensable treatment method in many cancer treatments. Hydrogels have the ability to absorb/desorb water thanks to their cross-links and 3-dimensional network structures. In order to eliminate the disadvantages of chemotherapy applications and to ensure that a sufficient dose of drug is given to the patient, targeted drug release technologies have been developed and hydrogels have come to the fore in this field. Natural polymeric hydrogels are widely used in the medical field. Chitosan(CS) natural biopolymer has been used in controlled drug release systems for many years due to its unique properties such as high biocompatibility, biodegradability and low toxicity. By using different natural biopolymers with CS, the swelling and drup uptake capacity properties of the hydrogels can be improved. In this article, the swelling and drug uptake capacity of CS, CS/HA and CS/HA/GEL hydrogels in the 5-Fluorouracil (5-FU) used as a model drug was evaluated and drug uptake capacities were determined by UV-Vis spectrophotometer. As a result, swelling and drug uptake capacities of CS, CS/HA and CS/HA/GEL hydrogels in anticancer drug solution were investigated. While the 5-FU retention capacity (1.2 mg 5-FU/g dry gel) increased with the addition of HA to CS, a decrease in 5-FU retention capacity (0.4 mg 5-FU/g dry gel) was observed with the addition of GEL to CS. All the prepared hydrogels are promising in future for controlled drug delivery sytems in biomedical applications.

Anahtar Kelimeler

Hydrogel, Hyaluronic acid, Drug retention, Gelatin, Chitosan, 5-FU

Kitosan/Hiyaluronik Asit/Jelatin Hidrojellerinin Antikanser İlacında Şişme Davranışı ve İlaç Tutma Kapasitesinin İncelenmesi

Öz

Günümüzde kanser teşhisi konulan hasta sayısı her geçen gün artmaktadır. Pek çok kanser tedavisinde kemoterapi vazgeçilmez tedavi yöntemidir. Kemoterapi uygulamalarının dezavantajlarını ortadan kaldırmak ve hastaya yeterli dozda ilaç verilmesinin sağlanması amacıyla hedefe yönelik ilaç salım teknolojileri geliştirilmiş ve hidrojeller bu alanda öne çıkmıştır. Hidrojeller, çapraz bağları ve 3-boyutlu ağ yapıları sayesinde su absorplama ve desorplama yeteneğine sahiptirler. Doğal polimerik hidrojeller tıp alanında yaygın olarak kullanılmaktadır. Kitosan(CS) doğal biyopolimeri, yüksek biyouyumluluk, biyobozunabilirlik ve düşük toksisite gibi benzersiz özellikleri nedeniyle uzun yıllardır kontrollü ilaç salım sistemlerinde kullanılmaktadır. Farklı doğal biyopolimerlerin CS ile sentezlenmesi ile oluşan hidrojellerin şişme ve ilaç tutma kapasitesi özellikleri geliştirilebilir. Bu makalede, CS’ye hyaluronik asit(HA) ve jelatin(GEL) ilave edilmesiyle geliştirilmiş yeni tip CS/HA/GEL hidrojellerinin model ilaç olarak kullanılan 5-Fluorourasil(5-FU) antikanser ilacındaki kütlece şişmeleri değerlendirilmiş, UV-Vis spektrofotometre ile 5-FU ilacı tutma kapasiteleri belirlenmiştir. Sonuç olarak, CS, CS/HA ve CS/HA/GEL hidrojellerinin antikanser ilacında şişme davranışı ve ilaç tutma kapasiteleri incelendi. CS’ye HA eklenmesiyle 5-FU tutma kapasitesi (1.2 mg 5-FU/g kuru jel) artarken CS’ye GEL ilave edilmesiyle ise 5-FU tutma kapasitesi (0.4 mg 5-FU/g kuru jel) azalma gözlenmiştir. Sentezlenen hidrojeller, biyomedikal alanda kontrollü ilaç salım sistemlerinde umut vadetmektedir.

Anahtar Kelimeler

Hidrojel, Hyaluronik asit, İlaç Tutma, Jelatin, Kitosan, 5-FU

Kaynakça

• Senapati, S., Mahanta, A. K., Kumar, S., & Maiti, P. (2018). Controlled drug delivery vehicles for cancer treatment and their performance. Signal transduction and targeted therapy, 3, 7.
• Reddy L. H. (2005). Drug delivery to tumours: recent strategies. The Journal of pharmacy and pharmacology, 57(10), 1231–1242.
• Dalwadi, C., & Patel, G. (2018). Thermosensitive nanohydrogel of 5-fluorouracil for head and neck cancer: preparation, characterization and cytotoxicity assay. International journal of nanomedicine, 13(T-NANO 2014 Abstracts), 31–33.
• Johnstone, R. W., Ruefli, A. A., & Lowe, S. W. (2002). Apoptosis: a link between cancer genetics and chemotherapy. Cell, 108(2), 153–164.
• Langer R. (1990). New methods of drug delivery. Science (New York, N.Y.), 249(4976), 1527–1533.
• Laftah, W.A., Hashim, S. and Ibrahim, A.N. (2011) Polymer Hydrogels: A Review. Polymer-Plastics Technology and Engineering, 50, 1475-1486.
• Slomkowski, S., Alemán, J. V., Gilbert, R. G., Hess, M., Horie, K., Jones, R. G., ... & Stepto, R. F. (2011). Terminology of polymers and polymerization processes in dispersed systems (IUPAC Recommendations 2011). Pure and Applied Chemistry, 83(12), 2229-2259.
• Hoffman, A. S. (2012). Hydrogels for biomedical applications. Advanced drug delivery reviews, 64, 18-23.
• Li, S., Jasim, A., Zhao, W., Fu, L., Ullah, M. W., Shi, Z., & Yang, G. (2018). Fabrication of pH-electroactive bacterial cellulose/polyaniline hydrogel for the development of a controlled drug release system. Materials & Manufacturing, 1(28), 41-49.
• Li, J., & Mooney, D. J. (2016). Designing hydrogels for controlled drug delivery. Nature Reviews Materials, 1(12), 1-17.
• Wu, Q., He, Z., Wang, X., Zhang, Q., Wei, Q., Ma, S., Ma, C., Li, J., & Wang, Q. (2019). Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy. Nature communications, 10(1), 240.
• Fang, Y., Tan, J., Lim, S., & Soh, S. (2018). Rupturing cancer cells by the expansion of functionalized stimuli-responsive hydrogels. NPG Asia Materials, 10(2), e465-e465.
• Yallapu, M. M., Jaggi, M., & Chauhan, S. C. (2011). Design and engineering of nanogels for cancer treatment. Drug discovery today, 16(9-10), 457–463.
• Norouzi, M., Nazari, B., & Miller, D. W. (2016). Injectable hydrogel-based drug delivery systems for local cancer therapy. Drug discovery today, 21(11), 1835–1849.
• Danhier, F., Feron, O., & Préat, V. (2010). To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. Journal of controlled release : Official journal of the Controlled Release Society, 148(2), 135–146.
• Thambi, T., Phan, V. H., & Lee, D. S. (2016). Stimuli-Sensitive Injectable Hydrogels Based on Polysaccharides and Their Biomedical Applications. Macromolecular rapid communications, 37(23), 1881–1896.
• Sun, Z., Song, C., Wang, C., Hu, Y., & Wu, J. (2020). Hydrogel-Based Controlled Drug Delivery for Cancer Treatment: A Review. Molecular pharmaceutics, 17(2), 373–391.
• Takimoto, C. H., & Awada, A. (2008). Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials. Cancer chemotherapy and pharmacology, 61(4), 535–548.
• Sharma, R., Raghav, R., Priyanka, K., Rishi, P., Sharma, S., Srivastava, S., & Verma, I. (2019). Exploiting chitosan and gold nanoparticles for antimycobacterial activity of in silico identified antimicrobial motif of human neutrophil peptide-1. Scientific reports, 9(1), 7866.
• Nejadshafiee, V., Naeimi, H., Goliaei, B., Bigdeli, B., Sadighi, A., Dehghani, S., Lotfabadi, A., Hosseini, M., Nezamtaheri, M. S., Amanlou, M., Sharifzadeh, M., & Khoobi, M. (2019). Magnetic bio-metal-organic framework nanocomposites decorated with folic acid conjugated chitosan as a promising biocompatible targeted theranostic system for cancer treatment. Materials science & engineering. C, Materials for biological applications, 99, 805–815.
• Sun, X., Liu, C., Omer, A. M., Yang, L. Y., & Ouyang, X. K. (2019). Dual-layered pH-sensitive alginate/chitosan/kappa-carrageenan microbeads for colon-targeted release of 5-fluorouracil. International journal of biological macromolecules, 132, 487–494.
• Smith, T., Affram, K., Bulumko, E., & Agyare, E. (2018). Evaluation of in-vitro cytotoxic effect of 5-FU loaded-chitosan nanoparticles against spheroid models. Journal of nature and science, 4(10), e535.
• Tian, B., Hua, S., Tian, Y., & Liu, J. (2020). Chemical and physical chitosan hydrogels as prospective carriers for drug delivery: A review. Journal of Materials Chemistry B, 8(44), 10050-10064.
• Miranda, D. G., Malmonge, S. M., Campos, D. M., Attik, N. G., Grosgogeat, B., & Gritsch, K. (2016). A chitosan-hyaluronic acid hydrogel scaffold for periodontal tissue engineering. Journal of biomedical materials research. Part B, Applied biomaterials, 104(8), 1691–1702.
• Collins, M. N., & Birkinshaw, C. (2013). Hyaluronic acid based scaffolds for tissue engineering: a review. Carbohydrate polymers, 92(2), 1262–1279.
• Lu, Z., Gao, J., He, Q., Wu, J., Liang, D., Yang, H., & Chen, R. (2017). Enhanced Antibacterial and Wound Healing Activities Of Microporous Chitosan-Ag/ZnO Composite Dressing. Carbohydrate polymers, 156, 460–469. Qiao, C., Ma, X., Zhang, J., & Yao, J. (2017). Molecular Interactions In Gelatin/Chitosan Composite Films. Food chemistry, 235, 45–50.
• Longley, D. B., Harkin, D. P., & Johnston, P. G. (2003). 5-fluorouracil: mechanisms of action and clinical strategies. Nature reviews. Cancer, 3(5), 330–338.
• Arias J. L. (2008). Novel strategies to improve the anticancer action of 5-fluorouracil by using drug delivery systems. Molecules (Basel, Switzerland), 13(10), 2340–2369.
• Feng, Y., Gao, Y., Wang, D., Xu, Z., Sun, W., & Ren, P. (2018). Autophagy Inhibitor (LY294002) and 5-fluorouracil (5-FU) Combination-Based Nanoliposome for Enhanced Efficacy Against Esophageal Squamous Cell Carcinoma. Nanoscale research letters, 13(1), 325.
• Salerno, A., Domingo, C., & Saurina, J. (2017). PCL foamed scaffolds loaded with 5-fluorouracil anti-cancer drug prepared by an eco-friendly route. Materials science & engineering. C, Materials for biological applications, 75, 1191–1197.
• Tummala, S., Satish Kumar, M. N., & Prakash, A. (2015). Formulation and characterization of 5-Fluorouracil enteric coated nanoparticles for sustained and localized release in treating colorectal cancer. Saudi pharmaceutical journal: SPJ: the official publication of the Saudi Pharmaceutical Society, 23(3), 308–314.
• Handali, S., Moghimipour, E., Kouchak, M., Ramezani, Z., Amini, M., Angali, K. A., Saremy, S., Dorkoosh, F. A., & Rezaei, M. (2019). New folate receptor targeted nano liposomes for delivery of 5-fluorouracil to cancer cells: Strong implication for enhanced potency and safety. Life sciences, 227, 39–50.
• Sun, L., Chen, Y., Zhou, Y., Guo, D., Fan, Y., Guo, F., Zheng, Y., & Chen, W. (2017). Preparation of 5-fluorouracil-loaded chitosan nanoparticles and study of the sustained release in vitro and in vivo. Asian journal of pharmaceutical sciences, 12(5), 418–423.
• Sun, X., Liu, C., Omer, A. M., Lu, W., Zhang, S., Jiang, X., Wu, H., Yu, D., & Ouyang, X. K. (2019). pH-sensitive ZnO/carboxymethyl cellulose/chitosan bio-nanocomposite beads for colon-specific release of 5-fluorouracil. International journal of biological macromolecules, 128, 468–479.
• Taşdelen, B., Erdoğan, S., & Bekar, B. (2018). Radiation synthesis and characterization of chitosan/hyraluronic acid/hydroxyapatite hydrogels: Drug uptake and drug delivery systems. Materials Today: Proceedings, 5(8), 15990-15997.
• Amini-Fazl, M. S., Mohammadi, R., & Kheiri, K. (2019). 5 Fluorouracil loaded chitosan/polyacrylic acid/Fe3O4 magnetic nanocomposite hydrogel as a potential anticancer drug delivery system. International journal of biological macromolecules, 132, 506–513.
• Mohammed, A. M., Osman, S. K., Saleh, K. I., & Samy, A. M. (2020). In Vitro Release of 5-Fluorouracil and Methotrexate from Different Thermosensitive Chitosan Hydrogel Systems. AAPS PharmSciTech, 21(4), 131.
• Emani, S., Vangala, A., Buonocore, F., Yarandi, N., & Calabrese, G. (2023). Chitosan Hydrogels Cross-Linked with Trimesic Acid for the Delivery of 5-Fluorouracil in Cancer Therapy. Pharmaceutics, 15(4), 1084.
• Güder, Ö.F., Taşdelen, B., Akyol, U. (2023). Doğal Polimer Bazlı Hidrojellerin Sentezi ve Karakterizasyonu. European Journal of Engineering and Applied Sciences, 6(2), 110-118.
• Lv, B., Bu, X., Da, Y., Duan, P., Wang, H., Ren, J., & Ma, J. (2020). Gelatin/PAM double network hydrogels with super-compressibility. Polymer, 210, 123021