In Vitro Antitumor Efficacy of Puerarin Nanosuspension against Human HepG2 Cells

Abstract:

Hepatocarcinoma, a malignant cancer, threaten human life badly. It is a current issue to seek the effective natural remedy from plant to treat cancer due to the resistance of the advanced hepatocarcinoma to chemotherapy. Puerarin (Pue), a major active ingredient in the traditional Chinese medicine Gegen, has a wide range of pharmacological properties and is considered to have anti-hepatocarcinoma effects. However its low oral bioavailability restricts its wide application. In this report, Pue-nanosuspension (Pue-NS) composed of Pue and poloxamer 188 was prepared by high pressure homogenization technique. The in vitro anti-hepatocarcinoma effects of Pue-NS relative to efficacy of bulk Pue were evaluated. The particle size and zeta potential of Pue-NS were 218.5 nm and −18.8 mV, respectively. MTT assay showed that Pue-NS effectively inhibited the proliferation of HepG2 cells, and the corresponding IC₅₀ values of Pue-NS and bulk Pue were 3.39 and 5.73 μg/ml. These results suggest that the delivery of Pue-NS is a promising approach for treating tumors.

• Periodical: Advanced Materials Research (Volume 1083)
• Pages: 27-31
• DOI: https://doi.org/10.4028/www.scientific.net/AMR.1083.27
• Online since: January 2015
• Authors: Wen Liang Lu, Hui Zhe Shi, Qun Zhou, Zhi Ping Wang*, Sheng Xiong, Yi Fei Wang, Yan Jun Zhang
• Keywords: Antitumor Activity, Cytotoxicity, HepG2 Cells, Nanosuspension, Puerarin

References

[1] D.M. Parkin，Global cancer statistics in the year 2000, Lancet Oncol. 2 (2001) 533-543.

[2] M.B. Thomas, & A.X. Zhu, Hepatocellular carcinoma: The need for progress, J. Clinic. Oncol. 23 (2005) 2892-2899.

[3] X.K. Deng, W. Yin, W.D. Li, F.Z. Yin, X.Y. Lu, & X.C. Zhang, The anti-tumor effects of alkaloids from the seeds of Strychnos nux-vomica on HepG2 cells and its possible mechanism, J. Ethnopharmacol. 106 (2006) 179-186.

DOI: 10.1016/j.jep.2005.12.021

[4] X.J. Li, & H.Y. Zhang, Western-medicine-validated anti-tumor agents and traditional Chinese medicine, Trends. Mol. Med. 14 (2008) 1-2.

DOI: 10.1016/j.molmed.2007.11.002

[5] X.P. Song, P.P. Chen, & X.S. Chai, Effects of puerarin on blood pressure and plasma rennin activity in spontaneously hypertensive rats, Acta Pharmacol Sinica. 9 (1988) 55-58.

[6] L. Gao, X. Ji, J. Song, P. Liu, F. Yan, W. Gong, S. Dang, & Y. Luo, Puerarin protects against ischemic brain injury in a rat model of transient focal ischemia, Neurol. Res. 31 (2009) 402-406.

DOI: 10.1179/174313209x444017

[7] S. Zhang, S. Chen, Y. Shen, D. Yang, X. Liu, A.C. Sun-Chi, & H. Xu, Puerarin induces angiogenesis in myocardium of rat with myocardial infarction, Biol. Pharm. Bull. 29 (2006) 945-950.

DOI: 10.1248/bpb.29.945

[8] F.L. Hsu, I.M. Liu, D.H. Kuo, W.C. Chen, H.C. Su, & J.T. Cheng, Antihyperglycemic effect of puerarin in streptozotocin-induced diabetic rats, J. Nat. Prod. 66 (2003) 788-792.

DOI: 10.1021/np0203887

[9] L.P. Yan, S.W. Chan, A.S.C. Chan, S.L. Chen, X.J. Ma, & H.X. Xu, Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats, Life Sci. 79 (2006).

DOI: 10.1016/j.lfs.2006.01.016

[10] Z.L. Yu, & W.J. Li, Induction of apoptosis by puerarin in colon cancer HT-29 cells, Cancer let. 238 (2006) 53-60.

DOI: 10.1016/j.canlet.2005.06.022

[11] T.T. Hien, H.G. Kim, E.H. Han, K.W. Kang, & H.G. Jeong, Molecular mechanism of suppression of MDR1 by puerarin from Pueraria lobata via NF-κB pathway and cAMP-responsive element transcriptional activity-dependent up-regulation of AMP-activated protein kinase in breast cancer MCF-7/adr cells, Mol. Nut. Food Res. 54 (2010).

DOI: 10.1002/mnfr.200900146

[12] Y.C. Wang, Y.Y. Ma, Y. Zheng, J. Song, X. Yang, C. Bi, D.R. Zhang, & Q. Zhang, In vitro and in vivo anticancer activity of a novel puerarin nanosuspension against colon cancer, with high efficacy and low toxicity, Int. J. Pharm. 441 (2013).

DOI: 10.1016/j.ijpharm.2012.10.021

[13] A. Fasano, Innovative strategies for the oral delivery of drugs and peptides, Trends Biotechnol. 16 (1998) 152-157.

DOI: 10.1016/s0167-7799(97)01170-0

[14] L.H. Wang, & Y.Y. Cheng, Solubility of puerarin in water, ethanol, and acetone from (288. 2 to 328. 2) K. J., Chem. Eng. Data. 50 (2005) 1375-1376.

DOI: 10.1021/je050076g

[15] D.Q. Quan, G.X. Xu, & X.G. Wu, Studies on preparation and absolute bioavailability of a self-emulsifying system containing puerarin, Chem. Pharm. Bull. 55 (2007) 800-803.

DOI: 10.1248/cpb.55.800

[16] S. Branchu, P.G. Rogueda, A.P. Plumb, & W.G. Cook, A decision-support tool for the formulation of orally active, poorly soluble compounds, Eur. J. Pharm. Sci. 32 (2007) 128-139.

DOI: 10.1016/j.ejps.2007.06.005

[17] B.G. Liu, J. Zhao, Y.H. Liu, X.A. Zhu, & J. Zeng, Physiochemical properties of the inclusion complex of puerarin and glucosyl-β-cyclodextrin, J. Agric. Food. Chem. 60 (2012) 12501-12507.

DOI: 10.1021/jf304447x

[18] J. Xie, F. Yang, X. Shi, X. Zhu, W. Su, & P. Wang, Improvement in solubility and bioavailability of puerarin by mechanochemical preparation, Drug. Dev. Ind. Pharm. 39 (2013) 825-836.

DOI: 10.3109/03639045.2012.664147

[19] A.H. Yu, H.G. Wang, J.L. Wang, F.L. Cao, Y. Gao, J. Cui, & G.X. Zhai, Formulation Optimization and Bioavailability After Oral and Nasal Administration in Rabbits of Puerarin-Loaded Microemulsion, J. Pharm. Sci. 100 (2011) 933-941.

DOI: 10.1002/jps.22333

[20] Y. Zhang, R.R. Wang, J. Wu, Q. Shen, Characterization and evaluation of self-microemulsifying sustained-release pellet formulation of puerarin for oral delivery, Int. J. Pharm. 427 (2012) 337-344.

DOI: 10.1016/j.ijpharm.2012.02.013

[21] C.F. Luo, M. Yuan, M.S. Chen, S.M. Liu, L. Zhu, B.Y. Huang, X.W. Liu, & W. Xiong, Pharmacokinetics, tissue distribution and relative bioavailability of puerarin solid lipid nanoparticles following oral administration, Int. J. Pharm. 410 (2011).

DOI: 10.1016/j.ijpharm.2011.02.064

[22] L.H. Xu, X. Tan, J.X. Yun, S.C. Shen, S.H. Zhang, C.M. Tu, W. Zhao, B. Tian, G.S. Yang, & K. J. Yao, Formulation of poorly water-soluble compound loaded solid lipid nanoparticles in a microchannel system fabricated by mechanical microcutting method: puerarin as a model drug, Ind. Eng. Chem. Res. 51 (2012).

DOI: 10.1021/ie300592u

[23] L.X. Zhao, A.C. Liu, M. Sun, J.S. Gu, H.G. Wang, S. Wang, J. Zhang, C.Y. Guo, R. Duan, & G.X. Zhai, Enhancement of Oral Bioavailability of Puerarin by Polybutylcyanoacrylate Nanoparticles, J. Nanomater. (2011) 126562.

DOI: 10.1155/2011/126562

[24] L. Gao, G.Y. Liu, J.L. Ma, X.Q. Wang, L. Zhou, X. Li, & F. Wang, Application of drug nanocrystal technologies on oral drug delivery of poorly soluble drugs, Pharm. Res. 30 (2013) 307-324.

DOI: 10.1007/s11095-012-0889-z

[25] C.G. Liversidge, & K.C. Cundy, Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I: absolute bioavailability of nanocrystalline danazol in beagle dogs, Int. J. Pharm. 125 (1995) 91-97.

DOI: 10.1016/0378-5173(95)00122-y

[26] D.R. Zhang, T.W. Tan, L. Gao, W. Zhao, & P. Wang, Preparation of azithromycin nanosuspensions by high pressure homogenization and its physicochemical characteristics studies, Drug. Dev. Ind. Pharm. 33 (2007) 569-575.

DOI: 10.1080/03639040600975147