Development and Optimization of Technetium-99m Radiolabeled Chitosan Nanoparticles for Potential Theranostic Applications in Cancer
Keywords:
chitosan, nanoparticles, ionic gelation, SPECT imaging, technetium-99m
Abstract
The appealing physical properties of 99mTc, such as its 6-hour half-life, emission of 140 keV gamma rays, and availability from affordable generators, have made its application preferable in SPECT imaging. The labelling of certain targeting moieties such as nanoparticles with 99mTc could improve the detection of diseased tissues for enhanced diagnosis and therapies. Chitosan nanoparticles which possess many appealing properties like biocompatibility and biodegradability, have been the focus of many scientific studies, demonstrating its use in various applications. In this study, chitosan nanoparticles were developed using the ionic gelation method, and the effect of concentration and pH of the medium on the size of the nanoparticles were evaluated. The nanoparticles produced were radiolabelled with 99mTc, which has a radioactivity range of between 100–111 MBq (2.7–3 mCi), and the stability of the radiolabelling was evaluated. The nanoparticles were found to be in the nanometres range, between 81 to 270 nm. The labeling efficiency of the 99mTc-labeled chitosan nanoparticles was determined to be higher than 90%, with more than 6 hours of stability. In conclusion, the 99mTc-radiolabelled chitosan-based radiopharmaceutical has shown good and promising characteristics and may be potentially useful as a dual-function theranostic agent in the future.
References
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Ruiz-Pulido, G., Quintanar-Guerrero, D., Serrano-Mora, L. E., & Medina, D. I. (2022). Triborheological Analysis of Reconstituted Gastrointestinal Mucus/Chitosan: TPP Nanoparticles System to Study Mucoadhesion Phenomenon under Different pH Conditions. Polymers, 14(22). https://doi.org/10.3390/polym14224978
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Elgebaly, R. H., Rageh, M. M., Adel, M., & Kamal, I. (2023). Studying Various Parameters Affecting Labeling Efficiency Of Radiopharmaceuticals In Nuclear Medicine. Journal of Pharmaceutical Negative Results ¦, 14(02), 3512–3520. https://doi.org/10.47750/pnr.2023.14.02.413
Gan, Q., Wang, T., Cochrane, C., & McCarron, P. (2005). Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids and Surfaces B: Biointerfaces, 44(2–3), 65–73. https://doi.org/10.1016/j.colsurfb.2005.06.001
Gundogdu, E., Ilem-Ozdemir, D., Ekinci, M., Ozgenc, E., & Asikoglu, M. (2015). Radiolabeling efficiency and cell incorporation of chitosan nanoparticles. Journal of Drug Delivery Science and Technology, 29, 84–89. https://doi.org/10.1016/j.jddst.2015.06.018
Hasan, S., & Prelas, M. A. (2020). Molybdenum-99 production pathways and the sorbents for 99Mo/99mTc generator systems using (n, γ) 99Mo: a review. SN Applied Sciences, 2(11), 1–28. https://doi.org/10.1007/s42452-020-03524-1
Hejjaji, E. M. A., Smith, A. M., & Morris, G. A. (2018). Evaluation of the mucoadhesive properties of chitosan nanoparticles prepared using different chitosan to tripolyphosphate (CS: TPP) ratios. International Journal of Biological Macromolecules, 120, 1610–1617. https://doi.org/10.1016/j.ijbiomac.2018.09.185
Hu, B., Pan, C., Sun, Y., Hou, Z., Ye, H., Hu, B., & Zeng, X. (2008). Optimization of fabrication parameters to produce chitosan-tripolyphosphate nanoparticles for delivery of tea catechins. Journal of Agricultural and Food Chemistry, 56(16), 7451–7458. https://doi.org/10.1021/jf801111c
Huang, M., Xu, Y., Xu, L., Bai, Y., & Xu, X. (2022). Interactions of water-soluble myofibrillar protein with chitosan: Phase behavior, microstructure, and rheological properties. Innovative Food Science and Emerging Technologies, 78. https://doi.org/10.1016/j.ifset.2022.103013
Ibrahim, Z., Hashim, Z., & Yaacob, B. (2011). Minimizing Molybdenum 99 contamination in Technetium 99m Pertechnetate from the elution of 99Mo/ 99m Tc Generator. NTC 2011: Nuclear Technical Convention 2011. http://inis.iaea.org/search/search.aspx?orig_q=RN:44122606
Kamal, R., Chadha, V. D., & Dhawan, D. K. (2018). Physiological uptake and retention of radiolabeled resveratrol loaded gold nanoparticles (99mTc-Res-AuNP) in colon cancer tissue. Nanomedicine: Nanotechnology, Biology, and Medicine, 14(3), 1059–1071. https://doi.org/10.1016/j.nano.2018.01.008
Katas, H., & Alpar, H. O. (2006). Development and characterization of chitosan nanoparticles for siRNA delivery. Journal of Controlled Release, 115(2), 216–225. https://doi.org/10.1016/j.jconrel.2006.07.021
Lima, K. O., Pinilla, C. M. B., Alemán, A., López-Caballero, M. E., Gómez-Guillén, M. C., Montero, P., & Prentice, C. (2021). Characterization, bioactivity and application of chitosan-based nanoparticles in a food emulsion model. Polymers, 13(19). https://doi.org/10.3390/polym13193331
Masarudin, M. J., Cutts, S. M., Evison, B. J., Phillips, D. R., & Pigram, P. J. (2015). Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: Application to the passive encapsulation of [14C]-doxorubicin. Nanotechnology, Science and Applications, 8, 67–80. https://doi.org/10.2147/NSA.S91785
Mattu, C., Li, R., & Ciardelli, G. (2013). Chitosan nanoparticles as therapeutic protein nanocarriers: The effect of ph on particle formation and encapsulation efficiency. Polymer Composites, 34(9), 1538–1545. https://doi.org/10.1002/pc.22415
Miftari, R., Maloku, H., Bajqinca, A., Rexhaj, B., Miftari, S., Kaqiu, Y., & Mansoob Khan, M. (2023). The Role of Dynamic (99m) Tc Pertechnetate Scintigraphy in Early Detection and Differentiation of Hyperthyroidism. Journal of Medicinal and Chemical Sciences, 6(9), 2177–2185. https://doi.org/10.26655/JMCHEMSCI.2023.9.23
Miladi, K., Sfar, S., Fessi, H., & Elaissari, A. (2015). Enhancement of alendronate encapsulation in chitosan nanoparticles. Journal of Drug Delivery Science and Technology, 30, 391–396. https://doi.org/10.1016/j.jddst.2015.04.007
Mirtajaddini, S. A., Najafi, M. F., Yazdi, S. A. V., & Oskuee, R. K. (2021). Preparation of Chitosan Nanoparticles as a Capable Carrier for Antigen Delivery and Antibody Production. Iranian Journal of Biotechnology, 19(4), 32–40. https://doi.org/10.30498/ijb.2021.247747.2871
Mushtaq, A., Rehman, T. U., Mansur, M. S., & Jehangir, M. (2008). Adsorption of99mTc-radiopharmaceuticals onto injection vials and syringes. Journal of Nuclear Medicine Technology, 36(2), 91–94. https://doi.org/10.2967/jnmt.107.048561
Nerli, G., Gonçalves, L. M. D., Cirri, M., Almeida, A. J., Maestrelli, F., Mennini, N., & Mura, P. A. (2023). Design, Evaluation, and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use. Pharmaceutics, 15(4). https://doi.org/10.3390/pharmaceutics15041305
Omar Zaki, S. S., Ibrahim, M. N., & Katas, H. (2015). Particle size affects concentration-dependent cytotoxicity of chitosan nanoparticles towards mouse hematopoietic stem cells. Journal of Nanotechnology, 2015. https://doi.org/10.1155/2015/919658
Rajabi, H., Rasaneh, S., & Salehi, S. (2016). Synthesis and Biological Evaluation of 99mTc-Chitosan Nanoparticles as a Potential Radiopharmaceutical for Liver Imaging. Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 46(10), 1450–1454. https://doi.org/10.1080/15533174.2015.1137010
Ribeiro, E. F., de Barros-Alexandrino, T. T., Assis, O. B. G., Junior, A. C., Quiles, A., Hernando, I., & Nicoletti, V. R. (2020). Chitosan and crosslinked chitosan nanoparticles: Synthesis, characterization and their role as Pickering emulsifiers. Carbohydrate Polymers, 250. https://doi.org/10.1016/j.carbpol.2020.116878
Rizvi, S. A. A., & Saleh, A. M. (2018). Applications of nanoparticle systems in drug delivery technology. In Saudi Pharmaceutical Journal (Vol. 26, Issue 1, pp. 64–70). Elsevier B.V. https://doi.org/10.1016/j.jsps.2017.10.012
Rosyada, A., Sunarharum, W. B., & Waziiroh, E. (2019). Characterization of chitosan nanoparticles as an edible coating material. IOP Conference Series: Earth and Environmental Science, 230(1). https://doi.org/10.1088/1755-1315/230/1/012043
Ruiz-Pulido, G., Quintanar-Guerrero, D., Serrano-Mora, L. E., & Medina, D. I. (2022). Triborheological Analysis of Reconstituted Gastrointestinal Mucus/Chitosan: TPP Nanoparticles System to Study Mucoadhesion Phenomenon under Different pH Conditions. Polymers, 14(22). https://doi.org/10.3390/polym14224978
Sullivan, D. J., Cruz-Romero, M., Collins, T., Cummins, E., Kerry, J. P., & Morris, M. A. (2018). Synthesis of monodisperse chitosan nanoparticles. Food Hydrocolloids, 83, 355–364. https://doi.org/10.1016/j.foodhyd.2018.05.010
Tang, Z.-X., Qian, J.-Q., & Shi, L.-E. (2007). Preparation of Chitosan Nanoparticles as Carrier for Immobilized Enzyme (Vol. 136).
Thakur, A., & Taranjit. (2011). Preparation of chitosan nanoparticles: A study of influencing factors. AIP Conference Proceedings, 1393, 299–300. https://doi.org/10.1063/1.3653728
Tian, B., Hua, S., & Liu, J. (2023). Multi-functional chitosan-based nanoparticles for drug delivery: Recent advanced insight into cancer therapy. In Carbohydrate Polymers (Vol. 315). Elsevier Ltd. https://doi.org/10.1016/j.carbpol.2023.120972
Zhuxin, L., Biao, Y., Badamkhand, D., Yifan, C., Honghong, S., Xiao, X., Mingqian, T., Zhixiang, W., & Chongjiang, C. (2023). Carboxylated chitosan improved the stability of phycocyanin under acidified conditions. International Journal of Biological Macromolecules, 233. https://doi.org/10.1016/j.ijbiomac.2023.123474
Zia, N., Iqbal, Z., Raza, A., Zia, A., Shafique, R., Andleeb, S., & Walker, G. C. (2022). Glycol-Chitosan-Based Technetium-99m-Loaded Multifunctional Nanomicelles: Synthesis, Evaluation, and In Vivo Biodistribution. Nanomaterials, 12(13). https://doi.org/10.3390/nano12132198
Published
2026-05-06
How to Cite
Abdul Aziz, A. F., Hamzah, F., Muchtaridi, M., & Mohd Gazzali, A. (2026). Development and Optimization of Technetium-99m Radiolabeled Chitosan Nanoparticles for Potential Theranostic Applications in Cancer. Indonesian Journal of Pharmacy, 37(2), 287-298. https://doi.org/10.22146/ijp.16994
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Research Article
