سنتز و مشخصه‌یابی نانوذرات لیپیدی جامد مغناطیسی بارگذاری شده با جمسیتابین: بهینه سازی پاسخ و مدل‌سازی با طراحی غربالگری قطعی

نوع مقاله : مقاله علمی پژوهشی

نویسندگان

1 گروه شیمی ، دانشکده علوم پایه، دانشگاه گیلان، رشت، ایران

2 گروه زیست شناسی، دانشکده علوم پایه، دانشگاه گیلان، رشت، ایران

چکیده

جمسیتابین (Gem) بهعنوان یک آنالوگ نوکلئوزیدی، عامل شیمی درمانی برای سرطان‌های سینه، مثانه و پانکراس است. مطالعه حاضر با هدف توسعه و بهینه‌سازی Gem-MSLNs، نانوذرات با بهبود تجمع داروها در بافت هدف می توانند عوارض جانبی کمتری ایجاد کنند. نانوذرات لیپیدی جامد مغناطیسی بارگذرای شده با جمسیتابین، برای به حداقل رساندن عوارض جانبی نامطلوب انجام شد. Gem-MSLNs به روش امولسیون‌سازی و تبخیر حلال سنتز شدند. یک طراحی غربالگری قطعی برای بهینه‌سازی فرمولاسیون Gem-MSLNs استفاده شد. اندازه ذرات و پتانسیل زتا و بازده به دام افتادن دارو در Gem-MSLNs به عنوان پاسخ مورد بررسی قرار گرفت. مشخصه‌یابی و ارزیابی Gem-MSLNs بهینه انجام شد. فرمولاسیون بهینه Gem-MSLNs دارای اندازه ذرات nm 36/4 ± 50/96، پتانسیل زتا mV3/0 ± 1/72+ و بازده به دام افتادن % 12/2 ± 10/21 بود این نتایج نشان می‌دهد که Gem-MSLNs پایداری کلوئیدی خوبی در محیط آبی دارند که از تجمع در طی فرآیندهای آزمایش جلوگیری می‌کند. بنابراین Gem-MSLNs گزینه‌های عالی برای استفاده‌های درمانی آینده هستند.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Synthesis and Characterization of Gemcitabine-Loaded Magnetic Solid Lipid Nanoparticles: Response Optimization and Modeling via Definitive Screening Designs

نویسندگان [English]

  • Aniseh Motamedifar 1
  • Hossein Ghafouri 2
  • Nina Alizadeh 1
1 Department of Chemistry, Faculty of Science, University of Guilan, Rasht, Iran
2 Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
چکیده [English]

Gemcitabine (Gem), as a nucleoside analog, is chemotherapy agent for breast, bladder, and pancreatic cancers. Nanoparticles can cause fewer unwanted side effects by improving the accumulation of drugs in the target tissue. The present study aimed to develop and optimize Gem-MSLNs, gemcitabine-loaded magnetic solid lipid nanoparticles, to minimizing undesired side effects. Gem-MSLNs were synthesized by emulsification and solvent evaporation methods. A definitive screening design was used to optimize the formulation of Gem-MSLNs. Particle size, zeta potential, and the entrapment efficiency of Gem-MSLNs were examined as responses. Characterizing and assessing the optimized Gem-MSLNs was done. The optimal formulation for Gem-MSLNs had a particle size of 96.50 ± 4.36 nm, zeta potential of +72.1 ± 0.3 mV, and an entrapment efficiency of 21.10 ± 2.12%. These results show that the Gem-MSLNs have good colloidal stability in an aqueous environment, which preventing aggregation during the experimentation processes. Gem-MSLNs are hence excellent options for upcoming therapeutic uses.

کلیدواژه‌ها [English]

  • Gemcitabine
  • solid lipid nanoparticles
  • cancer
  • magnetic nanoparticles
  • definitive screening design
[1] Birhanu, G., Javar, H. A., Seyedjafari, E., & Zandi-Karimi, A. (2017). Nanotechnology for delivery of gemcitabine to treat pancreatic cancer. Biomedicine & pharmacotherapy88, 635-643.
[2] Mader, M. Mary, H., James R., (2006), Antimetabolites, Comprehensive Medicinal Chemistry II, 7, 55-79.
[3] Martín-Banderas, L., Sáez-Fernández, E., Holgado, M. Á., Durán-Lobato, M. M., Prados, J. C., Melguizo, C., & Arias, J. L. (2013). Biocompatible gemcitabine-based nanomedicine engineered by Flow Focusing® for efficient antitumor activity. International journal of pharmaceutics443(1-2), 103-109.
[4] Celia, C., Cosco, D., Paolino, D., & Fresta, M. (2011). Gemcitabine-loaded innovative nanocarriers vs GEMZAR: biodistribution, pharmacokinetic features and in vivo antitumor activity. Expert Opinion on Drug Delivery8(12), 1609-1629.
[5] Paroha, S., Verma, J., Dubey, R. D., Dewangan, R. P., Molugulu, N., Bapat, R. A., Sahoo, P.K. & Kesharwani, P. (2021). Recent advances and prospects in gemcitabine drug delivery systems. International Journal of Pharmaceutics592, 120043.
[6] Manjunath, K., Reddy, J. S., & Venkateswarlu, V. (2005). Solid lipid nanoparticles as drug delivery systems. Methods Find Exp Clin Pharmacol27(2), 127-144.
[7] Tapeinos, C., Battaglini, M., & Ciofani, G. (2017). Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. Journal of Controlled Release264, 306-332.
[8] Tekade, R. K., Maheshwari, R., Tekade, M., & Chougule, M. B. (2017). Solid lipid nanoparticles for targeting and delivery of drugs and genes. In Nanotechnology-based approaches for targeting and delivery of drugs and genes (pp. 256-286). Academic Press.
[9] Affram, K. O., Smith, T., Ofori, E., Krishnan, S., Underwood, P., Trevino, J. G., & Agyare, E. (2020). Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells. Journal of drug delivery science and technology, 55, 101374.
[10] Emami, A., Ghafouri, H., & Sariri, R. (2023). Polyphyllin D-loaded solid lipid nanoparticles for breast cancer: Synthesis, characterization, in vitro, and in vivo studies. International Journal of Pharmaceutics639, 122976.
[11] Tran, T. H., Choi, J. Y., Ramasamy, T., Truong, D. H., Nguyen, C. N., Choi, H. G., Yong, C.S., Kim, J. O. (2014). Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells. Carbohydrate polymers, 114, 407-415.
[12] Zhao, S., Zhang, Y., Han, Y., Wang, J., & Yang, J. (2015). Preparation and characterization of cisplatin magnetic solid lipid nanoparticles (MSLNs): Effects of loading procedures of Fe3O4 nanoparticles. Pharmaceutical research, 32, 482-491.
[13] Oliveira, R. R., Carrião, M. S., Pacheco, M. T., Branquinho, L. C., de Souza, A. L. R., Bakuzis, A. F., & Lima, E. M. (2018). Triggered release of paclitaxel from magnetic solid lipid nanoparticles by magnetic hyperthermia. Materials Science and Engineering: C92, 547-553.
[14] Grillone, A., Riva, E.R., Mondini, A., Forte, C., Calucci, L., Innocenti, C., de Julian Fernandez, C., Cappello, V., Gemmi, M., Moscato, S., & Ronca, F. (2015). Active targeting of sorafenib: preparation, characterization, and in vitro testing of drug‐loaded magnetic solid lipid nanoparticles. Advanced healthcare materials4(11), 1681-1690.
[15] Haghighi Asl, A., Ahmadpour, A., & Fallah, N. (2017). Synthesis of Nano N-TiO2 for modeling of petrochemical industries spent caustic wastewater photocatalitic treatment in visible light using DOE method, Applied Chemistry, 12(42), 253-286. (in persian)
[16] Nabizadeh Chianeh, F., Mohammadi, B., & Asghari, A. (2017). Application of response surface methodology for optimizing removal of malachite green (MG) from aqueous solutions by natural zeolite. Applied Chemistry, 12(42), 209-222. (in persian)
[17] Dehghani Mobarake, M., Habibi, M., Faghihi Zarandi, A. (2019). New membrane based on Pd-SiO2 catalyst on PSS/NaX for hydrogen separation: Design and optimization. Applied Chemistry Today, 15(56), 131-148. (in persian)
[18] Lotfi, Z., Zavvar Mousavi, H., Sajjadi, S. M. (2020). Selective ultrasound enhanced removal of anionic dyes from binary mixture using multivariate calibration and central composite design modeling by positively charged hyper branched ammonium functionalized magnetic graphene oxide. Applied Chemistry Today, 14(53), 67-78. (in persian)
[19] Jannatdost, E., Tavakoli, A., Emamalisabzi, R., Kheiri, F. (2019). Synthesis of nanosized alumina templates with desired pores using Central Composite Design. Applied Chemistry Today, 15(55), 81-94. (in persian)
[20] Kazemi, H., Rajabi, M., Fahimirad, B., (2020). Application of response surface methodology for the photo degradation of dye using ZnO nanorods loaded on the activated carbon. Applied Chemistry Today, 14(53), 21-30. (in persian)
[21] Fekri, M. H., Saki, F., Razavi Mehr, M., Soleymani, S. (2024). Preparation of SBA-16 Silicate Nanoabsorbent by Green Method From Reed Plant Stem, Using it to Remove Phenolphthalein Pollutant and Investigating Effective Factors by RSM Method, Applied Chemistry Today, 18(68), 271-288. (in persian)
[22] Romić, M. D., Špoljarić, D., Klarić, M. Š., Cetina-Čižmek, B., Filipović-Grčić, J., & Hafner, A. (2019). Melatonin loaded lipid enriched chitosan microspheres–Hybrid dressing for moderate exuding wounds. Journal of Drug Delivery Science and Technology52, 431-439.
[23] Jones, B., & Nachtsheim, C. J. (2011). A class of three-level designs for definitive screening in the presence of second-order effects. Journal of Quality Technology43(1), 1-15.
[24] Ma, M., Zhang, Y., Yu, W., Shen, H. Y., Zhang, H. Q., & Gu, N. (2003). Preparation and characterization of magnetite nanoparticles coated by amino silane. Colloids and Surfaces A: physicochemical and engineering aspects212(2-3), 219-226.
[25] Wang, C., Li, B., Niu, W., Hong, S., Saif, B., Wang, S., Dong, C. & Shuang, S. (2015). β-Cyclodextrin modified graphene oxide–magnetic nanocomposite for targeted delivery and pH-sensitive release of stereoisomeric anti-cancer drugs. RSC advances5(108), 89299-89308.
[26] Soni, N., Soni, N., Pandey, H., Maheshwari, R., Kesharwani, P., & Tekade, R. K. (2016). Augmented delivery of gemcitabine in lung cancer cells exploring mannose anchored solid lipid nanoparticles. Journal of colloid and interface science481, 107-116.
[27] Venishetty, V. K., Samala, R., Komuravelli, R., Kuncha, M., Sistla, R., & Diwan, P. V. (2013). β-Hydroxybutyric acid grafted solid lipid nanoparticles: A novel strategy to improve drug delivery to brain. Nanomedicine: Nanotechnology, Biology and Medicine9(3), 388-397.
[28] Calucci, L., Grillone, A., Redolfi Riva, E., Mattoli, V., Ciofani, G., & Forte, C. (2017). NMR relaxometric properties of SPION-loaded solid lipid nanoparticles. The Journal of Physical Chemistry C121(1), 823-829.
[29] Nandini, P. T., Doijad, R. C., Shivakumar, H. N., & Dandagi, P. M. (2015). Formulation and evaluation of gemcitabine-loaded solid lipid nanoparticles. Drug delivery22(5), 647-651.
[30] Campos, J., Varas-Godoy, M., & Haidar, Z. S. (2017). Physicochemical characterization of chitosan-hyaluronan-coated solid lipid nanoparticles for the targeted delivery of paclitaxel: a proof-of-concept study in breast cancer cells. Nanomedicine12(5), 473-490.
[31] Tran, B. N., Nguyen, H. T., Kim, J. O., Yong, C. S., & Nguyen, C. N. (2017). Combination of a chemopreventive agent and paclitaxel in CD44-targeted hybrid nanoparticles for breast cancer treatment. Archives of pharmacal research40, 1420-1432.
[32] Gao, X., Zhang, J., Xu, Q., Huang, Z., Wang, Y., & Shen, Q. (2017). Hyaluronic acid-coated cationic nanostructured lipid carriers for oral vincristine sulfate delivery. Drug development and industrial pharmacy43(4), 661-667.
[33] Hassan, H., Bello, R. O., Adam, S. K., Alias, E., Meor Mohd Affandi, M. M. R., Shamsuddin, A. F., & Basir, R. (2020). Acyclovir-loaded solid lipid nanoparticles: Optimization, characterization and evaluation of its pharmacokinetic profile. Nanomaterials10(9), 1785.
[34] Trotta, M., Debernardi, F., & Caputo, O. (2003). Preparation of solid lipid nanoparticles by a solvent emulsification–diffusion technique. International journal of pharmaceutics257(1-2), 153-160.
[35] Mishra, V., Bansal, K. K., Verma, A., Yadav, N., Thakur, S., Sudhakar, K., & Rosenholm, J. M. (2018). Solid lipid nanoparticles: Emerging colloidal nano drug delivery systems. Pharmaceutics10(4), 191-212.
[36] Manjunath, K., Reddy, J. S., & Venkateswarlu, V. (2005). Solid lipid nanoparticles as drug delivery systems. Methods Find Exp Clin Pharmacol27(2), 127-144.
[37] Pate, K., & Safier, P. (2022). Chemical metrology methods for CMP quality. In Advances in chemical mechanical planarization (CMP) (pp. 355-383). Woodhead Publishing.
[38] Freitas, C., & Müller, R. H. (1998). Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN™) dispersions. International journal of pharmaceutics, 168(2), 221-229.
[39] Albuquerque, J., Moura, C. C., Sarmento, B., & Reis, S. (2015). Solid lipid nanoparticles: a potential multifunctional approach towards rheumatoid arthritis theranostics. Molecules, 20(6), 11103-11118.
[40] Delgado-Rosales, E. E., Quintanar-Guerrero, D., Piñón-Segundo, E., Magaña-Vergara, N. E., Leyva-Gómez, G., Martínez-Martínez, F. J., & Mendoza-Muñoz, N. (2018). Novel drug delivery systems based on the encapsulation of superparamagnetic nanoparticles into lipid nanocomposites. Journal of Drug Delivery Science and Technology46, 259-267.
[41] Tapeinos, C., Marino, A., Battaglini, M., Migliorin, S., Brescia, R., Scarpellini, A., ... & Ciofani, G. (2019). Stimuli-responsive lipid-based magnetic nanovectors increase apoptosis in glioblastoma cells through synergic intracellular hyperthermia and chemotherapy. Nanoscale11(1), 72-88.
[42] Chatterjee, S., Lee, M. W., & Woo, S. H. (2009). Influence of impregnation of chitosan beads with cetyl trimethyl ammonium bromide on their structure and adsorption of congo red from aqueous solutions. Chemical Engineering Journal155(1-2), 254-259.
[43] Pavia, D. L., Lampman, G. M., Kriz, G. S., & Vyvyan, J. A. (2014). Introduction to spectroscopy. Cengage learning.
[44] Kuligowski, J., Quintás, G., Esteve-Turrillas, F. A., Garrigues, S., & De la Guardia, M. (2008). On-line gel permeation chromatography–attenuated total reflectance–Fourier transform infrared determination of lecithin and soybean oil in dietary supplements. Journal of Chromatography A1185(1), 71-77.
[45] Michał, W., Ewa, D., & Tomasz, C. (2015). Lecithin-based wet chemical precipitation of hydroxyapatite nanoparticles. Colloid and polymer science293, 1561-1568