Synthesis of chitosan-graft-methacrylate with enhanced antimicrobial activity for improved mucoadhesive properties and controlled drug delivery systems
Article Sidebar
Main Article Content
Abstract
Chitosan (CS) is a derivative of chitin that displays antimicrobial effects and has other attributes that make it of interest for use in a variety of applications, including drug delivery systems. This study aimed to synthesize chitosan-graft-methacrylate (CS-g-MA) to improve the antimicrobial activities of CS for use in controlled drug delivery systems. CS-g-MA was synthesized via a nucleophilic acyl substitution reaction by gradually adding methacrylic anhydride (MA) to a CS solution until the ratio of CS to MA achieved the maximum degree of substitution. Proton nuclear magnetic resonance spectroscopy and attenuated total reflection-Fourier transformed infrared spectroscopy were used to characterize the resulting polymer. Its mucoadhesive capabilities and cytotoxicity toward human fibroblasts were evaluated, as well as its antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Candida albicans using the minimum inhibitory concentration and minimum bactericidal concentration tests. The optimized CS-g-MA polymer had an optimal weight CS:MA ratio of 3:4 and was combined with sodium fluorescein in tablet form to evaluate drug release. CS-g-MA improved the mucoadhesive capabilities of CS by increasing the number of intermolecular interactions with the grafted moiety. CS-g-MA was non-toxic to normal human fibroblasts and exhibited superior efficacy against S. aureus, E. coli, and C. albicans compared to CS. Furthermore, the CS-g-MA tablet regulated drug release for an extended period of more than 72 h. Thus, CS-g-MA shows significant potential for further development in advanced drug delivery systems.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Aranaz, I., Alcantara, A. R., Civera, M. C., Arias, C., Elorza, B., Heras Caballero, A., and Acosta, N. (2021). Chitosan: An overview of its properties and applications. Polymers (Basel), 13(19), 3256.
Bernkop-Schnürch, A., and Dünnhaupt, S. (2012). Chitosan-based drug delivery systems. European Journal of Pharmaceutics and Biopharmaceutics, 81(3), 463–469.
Collado-González, M., González Espinosa, Y., and Goycoolea, F. M. (2019). Interaction between chitosan and mucin: fundamentals and applications. Biomimetics (Basel), 4(2), 32.
Das, S. S., Kar, S., Singh, S. K., Verma, P. R. P., Hussain, A., and Beg, S. (2022). Chapter 2—Chitosan-based systems for oral drug delivery applications. In Chitosan in Drug Delivery (Hasnain, M. S., Beg, S., and Nayak, A. K., Eds.), pp. 23–53. Cambridge: Academic Press.
Dash, S., Murthy, P. N., Nath, L., and Chowdhury, P. (2010). Kinetic modeling on drug release from controlled drug delivery systems. Acta Poloniae Pharmaceutica, 67(3), 217–223.
Deusenbery, C., Wang, Y., and Shukla, A. (2021). Recent innovations in bacterial infection detection and treatment. ACS Infectious Diseases, 7(4), 695–720.
Heredia, N. S., Vizuete, K., Flores-Calero, M., Pazmino, V. K., Pilaquinga, F., Kumar, B., and Debut, A. (2022). Comparative statistical analysis of the release kinetics models for Nanoprecipitated drug delivery systems based on Poly(lactic-co-glycolic acid). PLoS One, 17(3), e0264825.
Ke, C. L., Deng, F. S., Chuang, C. Y., and Lin, C. H. (2021). Antimicrobial actions and applications of chitosan. Polymers (Basel), 13(6), 904.
Kenawy, E.-R., Abdel-Hay, F. I., El-Magd, A. A., and Mahmoud, Y. (2016). Biologically active polymers: Modification and anti-microbial activity of chitosan derivatives. Journal of Bioactive and Compatible Polymers, 20(1), 95–111.
Kolawole, O. M., Lau, W. M., and Khutoryanskiy, V. V. (2018). Methacrylated chitosan as a polymer with enhanced mucoadhesive properties for transmucosal drug delivery. International Journal of Pharmaceutics, 550(1–2), 123–129.
Kongkaoroptham, P., Piroonpan, T., and Pasanphan, W. (2021). Chitosan nanoparticles based on their derivatives as antioxidant and antibacterial additives for active bioplastic packaging. Carbohydrate Polymers, 257, 117610.
Kumar, M. N. V. R., Muzzarelli, R. A. A., Muzzarelli, C., Sashiwa, H., and Domb, A. J. (2004). Chitosan chemistry and pharmaceutical perspectives. Chemical Reviews, 104(12), 6017–6084.
Lam, H. T., Zupančič, O., Laffleur, F., and Bernkop-Schnürch, A. (2021). Mucoadhesive properties of polyacrylates: Structure—function relationship. International Journal of Adhesion and Adhesives, 107, 102857.
Li, B., Wang, L., Xu, F., Gang, X., Demirci, U., Wei, D., Li, Y., Feng, Y., Jia, D., and Zhou, Y. (2015). Hydrosoluble, UV-crosslinkable and injectable chitosan for patterned cell-laden microgel and rapid transdermal curing hydrogel in vivo. Acta Biomater, 22, 59–69.
Matica, M. A., Aachmann, F. L., Tondervik, A., Sletta, H., and Ostafe, V. (2019). Chitosan as a wound dressing starting material: Antimicrobial properties and mode of action. International Journal of Molecular Sciences, 20(23), 5889.
Cankaya, N. (2019). Grafting of chitosan: Structural, thermal and antimicrobial properties. Journal of the Chemical Society of Pakistan, 41(2), 240–245.
Pornpitchanarong, C., Rojanarata, T., Opanasopit, P., Ngawhirunpat, T., Bradley, M., and Patrojanasophon, P. (2022). Maleimide-functionalized carboxymethyl cellulose: A novel mucoadhesive polymer for transmucosal drug delivery. Carbohydrate Polymers, 288, 119368.
Rangsimawong, W., Opanasopit, P., Rojanarata, T., and Ngawhirunpat, T. (2014). Terpene-containing PEGylated liposomes as transdermal carriers of a hydrophilic compound. Biological and Pharmaceutical Bulletin, 37(12), 1936–1943.
Sahariah, P., and Masson, M. (2017). Antimicrobial chitosan and chitosan derivatives: a review of the structure-activity relationship. Biomacromolecules, 18(11), 3846–3868.
Shanmugam, A., Kathiresan, K., and Nayak, L. (2016). Preparation, characterization and antibacterial activity of chitosan and phosphorylated chitosan from cuttlebone of Sepia kobiensis (Hoyle, 1885). Biotechnology Reports, 9, 25–30.
Shariatinia, Z. (2019). Pharmaceutical applications of chitosan. Advances in Colloid and Interface Science, 263, 131–194.
Siti Zuhairah, Z., and Khuriah Abdul, H. (2021). Chitosan-based oral drug delivery system for peptide, protein and vaccine delivery. In Chitin and Chitosan - Physicochemical Properties and Industrial Applications (Berrada, M., Ed.), pp. 1–22. London: IntechOpen.
Sogias, I. A., Khutoryanskiy, V. V., and Williams, A. C. (2010). Exploring the factors affecting the solubility of chitosan in water. Macromolecular Chemistry and Physics, 211(4), 426–433.
Wang, H., Bu, X., Huang, Z., Yang, J., and Qiu, T. (2014). Synthesis of methacrylic anhydride by batch reactive distillation: Reaction kinetics and process. Industrial & Engineering Chemistry Research, 53(44), 17317–17324.
Wang, W., Meng, Q., Li, Q., Liu, J., Zhou, M., Jin, Z., and Zhao, K. (2020). Chitosan derivatives and their application in biomedicine. International Journal of Molecular Sciences, 21(2), 487.
Xing, K., Zhu, X., Peng, X., and Qin, S. (2014). Chitosan antimicrobial and eliciting properties for pest control in agriculture: A review. Agronomy for Sustainable Development, 35(2), 569–588.
Yu, L. M., Kazazian, K., and Shoichet, M. S. (2007). Peptide surface modification of methacrylamide chitosan for neural tissue engineering applications. Journal of Biomedical Materials Research Part A, 82(1), 243–255.