Preparation and Characterization of Chitosan/κ-Carrageenan Based Polymeric Nanoparticles for Gemcitabine Delivery

Preparation and Characterization of Chitosan/κ-Carrageenan Based Polymeric Nanoparticles for Gemcitabine Delivery

Cancer is the most fatal disease of the last century after cardiovascular disease. Gemcitabine is a nucleosideanalogue used in the treatment of cancer. However, like many anticancer drugs, it has many side effects thatlimit treatment. A nano drug delivery system has been developed to provide effective treatment by reducingside effects. Chitosan and κ-carrageenan, which are regarded as safe by the FDA, were used in the preparationof the nano drug delivery system. In the synthesis, pre-ionic gelation followed by polyelectrolyte complexationmethod was used and then a second ionic gelation step was added. Chitosan: κ-carrageenan ratio and CaCl2concentration were optimized and the optimum polymer ratio was determined as 6:1 and CaCl2 concentrationwas 2.5%. Its hydrodynamic size at optimum conditions was 393 nm and its size measured size in TEM was 20nm. FTIR analyzes showed that nanoparticle synthesis was successful. Drug loading was performed byencapsulation and 58% drug loading was achieved. After drug loading, the hydrodynamic dimension wasincreased to 595 nm and its size measured size in TEM 45 nm. Drug release was monitored for 95 hours andwas determined to be higher at pH 6.0 compared to 7.4 and pH sensitive. In addition, the Higuchi model is themost suitable mathematical model for drug release kinetics. The obtained results showed that chitosan: κcarrageenan nanoparticles were suitable for gemcitabine delivery and were pH sensitive enough to respond tothe tumor microenvironment.

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  • [1] Akbar, A. and Shakeel A., (2019). Marine Polysaccharides. Shakeel A. and Aisverya S. (Eds.), Carrageenans: Structure, Properties and Applications (pp. 29-52). Jenny Stanford Publishing, USA.
  • [2] Liu, J., Zhan, X., Wan, J., Wang, Y., & Wang, C. (2015). Review for carrageenan-based pharmaceutical biomaterials: Favourable physical features versus adverse biological effects. [Review]. Carbohydrate Polymers, 121, 27-36.
  • [3] Yanat, M., & Schroen, K. (2021). Preparation methods and applications of chitosan nanoparticles; with an outlook toward reinforcement of biodegradable packaging. [Article]. Reactive & Functional Polymers, 161.
  • [4] Mohammed, M., Syeda, J., Wasan, K., & Wasan, E. (2017). An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery. [Review]. Pharmaceutics, 9(4).
  • [5] Muxika, A., Etxabide, A., Uranga, J., Guerrero, P., & de la Caba, K. (2017). Chitosan as a bioactive polymer: Processing, properties and applications. [Review]. International Journal of Biological Macromolecules, 105, 1358-1368.
  • [6] Paroha, S., Verma, J., Dubey, R., Dewangan, R., Molugulu, N., Bapat, R., et al. (2021). Recent advances and prospects in gemcitabine drug delivery systems. [Review]. International Journal of Pharmaceutics, 592.
  • [7] Patra, J., Das, G., Fraceto, L., Campos, E., Rodriguez-Torres, M., Acosta-Torres, L., et al. (2018). Nano based drug delivery systems: recent developments and future prospects. [Review]. Journal of Nanobiotechnology, 16.
  • [8] Grenha, A., Gomes, M., Rodrigues, M., Santo, V., Mano, J., Neves, N., et al. (2010). Development of new chitosan/carrageenan nanoparticles for drug delivery applications. [Article]. Journal of Biomedical Materials Research Part a, 92A(4), 1265-1272.
  • [9] Rodrigues, S., da Costa, A., & Grenha, A. (2012). Chitosan/carrageenan nanoparticles: Effect of cross-linking with tripolyphosphate and charge ratios. [Article]. Carbohydrate Polymers, 89(1), 282-289.
  • [10] Ak, G., Bozkaya, U., Yilmaz, H., Turgut, O., Bilgin, I., Tomruk, C., et al. (2021). An intravenous application of magnetic nanoparticles for osteomyelitis treatment: An efficient alternative. [Article]. International Journal of Pharmaceutics, 592.
  • [11] Patil, J., Marapur, S., Gurav, P., Banagar, A., & Mishra, M. (2016). Ionotropic Gelation and Polyelectrolyte Complexation Technique Novel Approach to Drug Encapsulation. [Article|Book Chapter]. Handbook of Encapsulation and Controlled Release, 273-296.
  • [12] Daniel-da-Silva, A. L., Ferreira, L. u., Gil, A. M., & Trindade, T. (2011). Synthesis and swelling behavior of temperature responsive κ-carrageenan nanogels. Journal of Colloid and Interface Science, 35(2), 512-517.
  • [13] Pedroso-Santana, S., & Fleitas-Salazar, N. (2020). Ionotropic gelation method in the synthesis of nanoparticles/microparticles for biomedical purposes. [Review]. Polymer International, 69(5), 443-447.
  • [14] Lankalapalli, S., & Kolapalli, V. (2009). Polyelectrolyte complexes: A review of their applicability in drug delivery technology. [Review]. Indian Journal of Pharmaceutical Sciences, 71(5), 481-487.
  • [15] Triwulandari, E., Fahmiati, S., Sampora, Y., Meliana, Y., Ghozali, M., Sondari, D., et al. (2018). Effect of Polyanions Variation on The Particle Size of Chitosan Nanoparticle Prepared by Ionic Gelation Method. [Proceedings Paper]. Proceedings of the 4th International Symposium on Applied Chemistry 2018, 2024.
  • [16] Yew, H.-C., & Misran, M. (2016). Preparation and characterization of pH dependent κ-carrageenan-chitosan nanoparticle as potential slow release delivery carrier. Iranian Polymer Journal, 25, 1037-1046.
  • [17] Wathoni, N., Meylina, L., Rusdin, A., Abdelwahab Mohammed, A.F., Tirtamie, D., Herdiana, Y., Motoyama, K., Panatarani, C., Joni, I.M., Lesmana, R., Muchtaridi, M. (2021). The Potential Cytotoxic Activity Enhancement of α-Mangostin in Chitosan-Kappa Carrageenan-Loaded Nanoparticle against MCF-7 Cell Line. Polymers, 13(11), 1681 - 1694.
  • [18] Dash, S., Murthy, P.N., Nath, L., Chowdhury, P. (2010). Kinetic Modeling on Drug Release from Controlled Drug Delivery System. Acta Poloniae Pharmaceutica - Drug Research, 67(3), 217-223.
  • [19] Amgoth, C., Phan, C., Banavoth, M., Rompivalasa, S., & Tang, G. (2019). Polymer Properties: Functionalization and Surface Modified Nanoparticles. In R. K. Tyagi, N. Garg, R. Shukla, & P. S. Bisen (Eds.), Role of Novel Drug Delivery Vehicles in Nanobiomedicine. IntechOpen. https://doi.org/10.5772/intechopen.84424.
  • [20] Sogias, I.A., Khutoryanskiy, V.V., Williams, A.C. (2010). Exploring the Factors Affecting the Solubility of Chitosan in Water. [Article]. Macromolecular Chemistry and Physics, 211(4), 426 - 433.
  • [21] Distantina, S., Rochmadi, Fahrurrozi, M. Wiratni. (2014). Stabilization of Kappa Carrageenan Film by Crosslinking: Comparison of Glutaraldehyde and Potassium Sulphate as the Crosslinker. 2014 5th International Conference on Chemical Engineering and Applications, 74, 5pp.
Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi-Cover
  • ISSN: 1307-9085
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2008
  • Yayıncı: Erzincan Binali Yıldırım Üniversitesi, Fen Bilimleri Enstitüsü