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

Year 2022, , 636 - 648, 31.08.2022
https://doi.org/10.18185/erzifbed.1134093

Abstract

Cancer is the most fatal disease of the last century after cardiovascular disease. Gemcitabine is a nucleoside
analogue used in the treatment of cancer. However, like many anticancer drugs, it has many side effects that
limit treatment. A nano drug delivery system has been developed to provide effective treatment by reducing
side effects. Chitosan and κ-carrageenan, which are regarded as safe by the FDA, were used in the preparation
of the nano drug delivery system. In the synthesis, pre-ionic gelation followed by polyelectrolyte complexation
method was used and then a second ionic gelation step was added. Chitosan: κ-carrageenan ratio and CaCl2
concentration were optimized and the optimum polymer ratio was determined as 6:1 and CaCl2 concentration
was 2.5%. Its hydrodynamic size at optimum conditions was 393 nm and its size measured size in TEM was 20
nm. FTIR analyzes showed that nanoparticle synthesis was successful. Drug loading was performed by
encapsulation and 58% drug loading was achieved. After drug loading, the hydrodynamic dimension was
increased to 595 nm and its size measured size in TEM 45 nm. Drug release was monitored for 95 hours and
was determined to be higher at pH 6.0 compared to 7.4 and pH sensitive. In addition, the Higuchi model is the
most 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 to
the tumor microenvironment.

Supporting Institution

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Project Number

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Thanks

I acknowledge to Prof. Dr. Şenay Hamarat Şanlıer for allowing me to use her laboratory equipment and consumables.

References

  • [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.
Year 2022, , 636 - 648, 31.08.2022
https://doi.org/10.18185/erzifbed.1134093

Abstract

Project Number

Mevcut değildir.

References

  • [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.
There are 21 citations in total.

Details

Primary Language English
Subjects Engineering
Journal Section Makaleler
Authors

Habibe Yılmaz 0000-0003-1106-0458

Project Number Mevcut değildir.
Publication Date August 31, 2022
Published in Issue Year 2022

Cite

APA Yılmaz, H. (2022). Preparation and Characterization of Chitosan/κ-Carrageenan Based Polymeric Nanoparticles for Gemcitabine Delivery. Erzincan University Journal of Science and Technology, 15(2), 636-648. https://doi.org/10.18185/erzifbed.1134093