Surface Charge Effect of Furazolidone-loaded Polymeric Mixed Micelles for Delivery to Breast Cancer Cells (MCF-7) and Hepatocellular Carcinoma Cells (HepG2)

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Watcharaphong Chaemsawang
Putthiporn Khongkaew

Abstract

Nano drug delivery systems are important strategies to increase the specificity toward cancer cells as well as reduce the side effects of an administered drug. The purpose of this research was to study the effect of the charge of the polymeric micelle on the delivery of furazolidone into cancer cells. To be used as a guideline to develop anti-cancer pharmaceutical products with solubility problems. Material and Method: a drug delivery system was developed in the form of polymeric micelles prepared from the poloxamer 407 with Hexadecyltrimethylammonium bromide(CTAB) or lecithin, and loaded with furazolidone for delivery to breast cancer cells (MCF-7) and hepatocyte carcinoma (Hep G2) using a thin-film hydration method. Each formulation was prepared to compare the effect of the ions on the surface of two surfactants by considering the parameters of physical properties, particle size, particle size distribution and entrapment efficiency. Results: the results showed that optimal cationic and anionic formulations comprised the poloxamer 407: CTAB ratio of 200 mg:20 mg (particle size of about 307.14 ± 62.01 nm, zeta potential 22.36 ± 7.97 mV and entrapment efficiency 62.26 ± 1.49%), and the poloxamer 407: lecithin ratio of 200 mg:4 mg (particle size of about 311.42 ± 32.42 nm, zeta potential -22.34 ± 1.31 mV and entrapment efficiency 57.47 ± 3.14%). The selected formulations were then evaluated for cell cytotoxicity and cellular uptake of MCF-7 and Hep G2. Conclusion: From the experimental data, it was found that the surface charge of the drug delivery system is a factor that affects the treatment efficiency. Each type of cancer responds differently to the surface charge. For example, liver cancer cells have a higher rate of uptake of polar-substances than breast cancer cells.  However, this study is a study of factors that affect the delivery of the substance to cancer cells. It may need to be tested in other types of cancer cells and will test toxicity with normal cells in the future.

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Pharmaceutical Sciences

References

Ahmed, M. and Narain, R. (2013). Cell line dependent uptake and transfection efficiencies of PEI–anionic glycopolymer systems. Biomaterials, 34, 4368-4376.

Alam, M. I., Paget, T. and Elkordy, A. A. (2016). Formulation and advantages of furazolidone in liposomal drug delivery systems. European Journal of Pharmaceutical Sciences, 84, 139-145.

Bnyan, R., Khan, I., Ehtezazi, T., Saleem, I., Gordon, S., O'Neill, F. and Roberts, M. (2018). Surfactant effects on lipid-based vesicles properties. Journal of pharmaceutical sciences, 107, 1237-1246.

Carraher, C. E., Roner, M. R., Thibodeau, R. and Johnson, A. M. (2014). Synthesis, structural characterization, and preliminary cancer cell study results for poly(amine esters) derived from triphenyl-group VA organometallics and norfloxacin. Inorganica Chimica Acta, 423, 123-131.

Chaemsawang, W., Prasongchean, W., Papadopoulos, K. I., Ritthidej, G., Sukrong, S. and Wattanaarsakit, P. (2019). The Effect of Okra (Abelmoschus esculentus (L.) Moench) Seed Extract on Human Cancer Cell Lines Delivered in Its Native Form and Loaded in Polymeric Micelles. International journal of biomaterials, 2019, 9404383-9404383.

Chat, O. A., Najar, M. H., Mir, M. A., Rather, G. M. and Dar, A. A. (2011). Effects of surfactant micelles on solubilization and DPPH radical scavenging activity of Rutin. Journal of Colloid and Interface Science, 355, 140-149.

Croy, S. and Kwon, G. (2006). Polymeric micelles for drug delivery. Current pharmaceutical design, 12, 4669-4684.

Deng, S., Tang, S., Dai, C., Zhou, Y., Yang, X., Li, D. and Xiao, X. (2016). P21Waf1/Cip1 plays a critical role in furazolidone-induced apoptosis in HepG2 cells through influencing the caspase-3 activation and ROS generation. Food and Chemical Toxicology, 88, 1-12.

Djekic, L., Čalija, B. and Medarević, Đ. (2020). Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug. Journal of Molecular Liquids, 303, 112639.

Djekic, L., Krajisnik, D., Martinovic, M., Djordjevic, D. and Primorac, M. (2015). Characterization of gelation process and drug release profile of thermosensitive liquid lecithin/poloxamer 407 based gels as carriers for percutaneous delivery of ibuprofen. International Journal of Pharmaceutics, 490, 180-189.

Dwiastuti, R., Noegrohati, S., Istyastono, E. P. and Marchaban. Year. Formulation and physical properties observations of soy lecithin liposome containing 4-n-butylresorcinol. In: AIP Conference Proceedings, 2016. AIP Publishing, 160005.

Farnia, P., Velayati, A. A., Mollaei, S. and Ghanavi, J. (2017). Modified rifampin nanoparticles: Increased solubility with slow release rate. International journal of mycobacteriology, 6, 171.

Hingmire, S., Oulkar, D. P., Utture, S. C., Ahammed Shabeer, T. P. and Banerjee, K. (2015). Residue analysis of fipronil and difenoconazole in okra by liquid chromatography tandem mass spectrometry and their food safety evaluation. Food Chemistry, 176, 145-151.

Jiang, X., Sun, L., Qiu, J. J., Sun, X., Li, S., Wang, X., So, C. W. E. and Dong, S. (2013). A Novel Application of Furazolidone: Anti-Leukemic Activity in Acute Myeloid Leukemia. PLoS ONE, 8, e72335.

Jin, X., Tang, S., Chen, Q., Zou, J., Zhang, T., Liu, F., Zhang, S., Sun, C. and Xiao, X. (2011). Furazolidone induced oxidative DNA damage via up-regulating ROS that caused cell cycle arrest in human hepatoma G2 cells. Toxicology Letters, 201, 205-212.

Jin, X., Zhang, Y., Zhang, Z., Che, D. and Lv, H. (2016). Juglone loaded poloxamer 188/phospholipid mixed micelles evaluated in vitro and in vivo in breast cancer. International Journal of Pharmaceutics, 515, 359-366.

Kalbáčová, M., Verdánová, M., Mravec, F., Halasová, T. and Pekař, M. (2014). Effect of CTAB and CTAB in the presence of hyaluronan on selected human cell types. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 460, 204-208.

Khalil, R. A. and Al-hakam, A. Z. (2014). Theoretical estimation of the critical packing parameter of amphiphilic self-assembled aggregates. Applied Surface Science, 318, 85-89.

Lanta, Q., Arveux, P. and Asselain, B. (2019). [Epidemiology and socio-cultural specificities of young women with breast cancer]. Bull Cancer, 106, S4-s9.

Lewkowski, J., Rogacz, D. and Rychter, P. (2019). Hazardous ecotoxicological impact of two commonly used nitrofuran-derived antibacterial drugs: Furazolidone and nitrofurantoin. Chemosphere, 222, 381-390.

Lu, Y. and Park, K. (2013). Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. International journal of pharmaceutics, 453, 198-214.

Ma, Y., Zhuang, Y., Xie, X., Wang, C., Wang, F., Zhou, D., Zeng, J. and Cai, L. (2011). The role of surface charge density in cationic liposome-promoted dendritic cell maturation and vaccine-induced immune responses. Nanoscale, 3, 2307-2314.

Mahbub, S., Molla, M. R., Saha, M., Shahriar, I., Hoque, M. A., Halim, M. A., Rub, M. A., Khan, M. A. and Azum, N. (2019). Conductometric and molecular dynamics studies of the aggregation behavior of sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) in aqueous and electrolytes solution. Journal of Molecular Liquids.

Mandal, A., Bisht, R., Rupenthal, I. D. and Mitra, A. K. (2017). Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies. Journal of Controlled Release, 248, 96-116.

Meena, R., Kumar, S., kumar, R., Gaharwar, U. S. and Rajamani, P. (2017). PLGA-CTAB curcumin nanoparticles: Fabrication, characterization and molecular basis of anticancer activity in triple negative breast cancer cell lines (MDA-MB-231 cells). Biomedicine & Pharmacotherapy, 94, 944-954.

P.R, S., James, N. R., Kumar P.R, A. and K. Raj, D. (2016). Galactosylated alginate-curcumin micelles for enhanced delivery of curcumin to hepatocytes. International Journal of Biological Macromolecules, 86, 1-9.

Pashirova, T. N., Zhukova, N. A., Lukashenko, S. S., Valeeva, F. G., Burilova, E. A., Sapunova, A. S., Voloshina, A. D., Mirgorodskaya, A. B., Zakharova, L. Y., Sinyashin, O. G. and Mamedov, V. A. (2019). Multi-targeted approach by 2-benzimidazolylquinoxalines-loaded cationic arginine liposomes against сervical cancer cells in vitro. Colloids and Surfaces B: Biointerfaces, 178, 317-328.

Pellosi, D. S., Tessaro, A. L., Moret, F., Gaio, E., Reddi, E., Caetano, W., Quaglia, F. and Hioka, N. (2016). Pluronic® mixed micelles as efficient nanocarriers for benzoporphyrin derivatives applied to photodynamic therapy in cancer cells. Journal of Photochemistry and Photobiology A: Chemistry, 314, 143-154.

Salahuddin, N., Abdelwahab, M., Gaber, M. and Elneanaey, S. (2020). Synthesis and Design of Norfloxacin drug delivery system based on PLA/TiO2 nanocomposites: Antibacterial and antitumor activities. Materials Science and Engineering: C, 108, 110337.

Salatin, S. and Yari Khosroushahi, A. (2017). Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles. Journal of cellular and molecular medicine, 21, 1668-1686.

Saxena, V. and Hussain, M. D. (2013). Polymeric mixed micelles for delivery of curcumin to multidrug resistant ovarian cancer. Journal of biomedical nanotechnology, 9, 1146-1154.

Sokolova, V., Kozlova, D., Knuschke, T., Buer, J., Westendorf, A. M. and Epple, M. (2013). Mechanism of the uptake of cationic and anionic calcium phosphate nanoparticles by cells. Acta Biomaterialia, 9, 7527-7535.

Wang, H., Lai, Y.-J., Chan, Y.-L., Li, T.-L. and Wu, C.-J. (2011). Epigallocatechin-3-gallate effectively attenuates skeletal muscle atrophy caused by cancer cachexia. Cancer Letters, 305, 40-49.

Xie, M., Zhang, F., Liu, L., Zhang, Y., Li, Y., Li, H. and Xie, J. (2018). Surface modification of graphene oxide nanosheets by protamine sulfate/sodium alginate for anti-cancer drug delivery application. Applied Surface Science, 440, 853-860.

Zhang, H. X., Du, G. H. and Zhang, J. T. (2004). Assay of mitochondrial functions by resazurin in vitro. Acta Pharmacol Sin, 25, 385-9.