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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (6): 674-680.doi: 10.3736/jcim20120612

• Original Experimental Research • Previous Articles     Next Articles

A comparison study of pharmacokinetics between bufalin-loaded bovine serum albumin nanoparticles and bufalin in rats

Hui-qing Zhang1,2, Zi-fei Yin2, Jia-yu Sheng1,2, Zhu-qian Jiang1,2, Bao-yu Wu1,2, Yong-hua Su2()   

  1. 1. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
  • Received:2012-03-22 Accepted:2012-04-10 Online:2012-06-20 Published:2018-06-15
  • Contact: Su Yong-hua E-mail:suyh2001@126.com

Objective: To determine the bufalin concentration in rats’ plasma by establishing a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and to evaluate and compare the pharmacokinetic characteristics of bufalin-loaded bovine serum albumin nanoparticles (bufalin-BSA-NP) and bufalin.
Methods: Thirty Wistar rats were randomly divided into six groups with five rats in each group, and administered with a single dose of 0.6, 0.3 and 0.15 mg/kg of bufalin-BSA-NP or bufalin, respectively. After the administration, blood samples were collected from the orbital venous plexus at designed time points (1, 5, 8, 10, 15, 20, 30, 45, 60, 120, 180, 300 and 480 min). The concentration of bufalin in plasma at different sampling time points was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and compared.
Results: The established HPLC-MS/MS method had high linearity, precision and accuracy. The blood plasma area under curve, the mean retention time and the terminal half life of bufalin-BSA-NP were 1.19 to 1.81, 2.12 to 3.61 and 2.17 to 2.94 times of bufalin, respectively.
Conclusion: Bufalin-BSA-NP has the function of sustained release thus to prolong the bufalin remaining in blood.

Key words: bufalin, nanoparticles, pharmacokinetics, chromatography, high-pressure liquid, tandem mass spectrometry, rats

Figure 1

Chemical structure of bufalin (A) and cinobufagin (B)"

Figure 2

Product irons of bufalin (A) and cinobufagin (B, internal standard)"

Figure 3

HPLC-MS/MS chromatograms of bufalin A: a blank plasma; B: a blank plasma sample spiked with bufalin and IS; C: plasma sample collected from a rat 15 min after intravenous administration of bufalin at a dose of 0.3 mg/kg. IS: internal standard; MRM: multiple reactions monitoring; HPLC-MS/MS: high-performance liquid chromatography-tandem mass spectrometry."

Figure 4

Mean plasma concentration-time curve of bufalin in rats after a single dose of 0.6 (A), 0.3 (B) or 0.15 mg/kg (C) Data are represented as mean±standard division, n=5. Bufalin-BSA-NP: bufalin-loaded bovin serum albumin nanoparticle."

Table 1

Pharmacokinetic parameters of bufalin and bufalin-BSA-NP in rats after a single dose of 0.6, 0.3 or 0.15 mg/kg"

Group Dose
(mg/kg)
Cmax
(ng/mL)
t1/2
(min)
MRT
(min)
AUC0~8
(ng·h/mL)
AUC0~∞
(ng·h/mL)
Vd
(L/kg)
CL
(L/(h·kg))
Bufalin 0.6 2 430.5 43.2 19.2 299.7 302.60 0.64 2.00
0.3 682.3 39.0 24.6 126.6 128.22 0.95 2.34
0.15 515.6 34.8 24.0 77.6 78.53 0.76 1.93
Bufalin-BSA-NP 0.6 2 186.2 127.2 68.4 380.8 389.70 1.76 1.54
0.3 599.9 93.0 88.8 229.6 233.48 1.90 1.29
0.15 474.3 75.6 51.0 92.5 94.98 1.34 1.58
[1] Gu W, Han KQ, Su YH, Huang XQ, Ling CQ . Inhibition action of bufalin on human transplanted hepatocellular tumor and its effects on expressions of Bcl-2 and Bax proteins in nude mice[J]. J Chin Integr Med, 2007,5(2):155-159
顾伟, 韩克起, 苏永华, 黄雪强, 凌昌全 . 蟾毒灵对裸鼠人肝癌移植瘤的抑制作用及对Bcl-2和Bax蛋白表达的影响[J]. 中西医结合学报, 2007,5(2):155-159
[2] Jiang Y, Zhang Y, Luan J, Duan H, Zhang F, Yagasaki K, Zhang G . Effects of bufalin on the proliferation of human lung cancer cells and its molecular mechanisms of action[J]. Cytotechnology, 2010,62(6):573-583
doi: 10.1007/s10616-010-9310-0
[3] Xie CM, Chan WY, Yu S, Zhao J, Cheng CH . Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation[J]. Free Radic Biol Med, 2011,51(7):1365-1375
doi: 10.1016/j.freeradbiomed.2011.06.016
[4] Qi F, Li A, Inagaki Y, Kokudo N, Tamura S, Nakata M, Tang W . Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor[J]. Int Immunopharmacol, 2010,11(3):342-349
[5] Su YH, Ling CQ. Bufalin-loaded bovine serum albumin nanoparticle and its preparation method. China, 200510110061.4. 2006-05-17. Bufalin-loaded bovine serum albumin nanoparticle and its preparation method. China, 200510110061.4. 2006-05-17. .
苏永华, 凌昌全 . 蟾毒灵白蛋白纳米粒制剂及其制备方法. 中国, 200510110061.4. 2006-05-17. 蟾毒灵白蛋白纳米粒制剂及其制备方法. 中国, 200510110061.4. 2006-05-17. .
[6] Sun N . Quantitative analysis, preclinical pharmacokinetics and toxicikinetics of MCC-555 in biological matrix[M]. Shanghai: Second Military Medical University, 2006: 32-33
孙宁 . 生物样品中MCC-555定量分析及临床前药代动力学与毒代动力学研究[M]. 上海: 第二军医大学, 2006: 32-33
[7] Cao Y, Zhao L, Liang Q, Bi K, Wang Y, Luo G . Study of the determination and pharmacokinetics of bufadienolides in dog’s plasma after administration of Liu-Shen-Wan by high performance liquid chromatography time-of-flight mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2007,853(12):227-233
doi: 10.1016/j.jchromb.2007.03.018
[8] Zhang Y, Tang X, Liu X, Li F, Lin X . Simultaneous determination of three bufadienolides in rat plasma after intravenous administration of bufadienolides extract by ultra performance liquid chromatography electrospray ionization tandem mass spectrometry[J]. Anal Chim Acta, 2008,610(2):224-231
doi: 10.1016/j.aca.2008.01.029
[9] Liang Y, Liu AH, Qin S, Sun JH, Yang M, Li P, Guo DA . Simultaneous determination and pharmacokinetics of five bufadienolides in rat plasma after oral administration of Chansu extract by SPE-LC method[J]. J Pharm Biomed Anal, 2008,46(2):442-448
doi: 10.1016/j.jpba.2007.11.001
[10] Liu D, Du SY, He XF, Wang AG, Li N . Studies on simultaneous determination and pharmacokinetics of two bufadienolides in rabbits plasma[J]. Zhongguo Shi Yan Fang Ji Xue Za Zhi, 2011,17(21):135-138
刘冬, 杜守颖, 何秀峰, 王爱国, 李娜 . 蟾酥提取物中2种蟾蜍甾烯类成分兔体内药代动力学研究[J]. 中国实验方剂学杂志, 2011,17(21):135-138
[11] Study Group of Research Guidelines for Non-clinical Pharmacokinetic Evaluation of Chemical Drugs. Research guidelines for non-clinical pharmacokinetic evaluation of chemical drugs. [H]GPT5-1. 2005. Chinese.
《化学药物非临床药代动力学研究技术指导原则》课题研究组. 化学药物非临床药代动力学研究技术指导原则.[H]GPT5- 1. 2005.
[12] Wang Y, Li Q, Cao WJ . Research advance of nanometric traditional Chinese herbal drugs for cancer treatment[J]. J Chin Integr Med, 2007,5(6):697-701
王炎, 李琦, 曹伟家 . 纳米中药治疗肿瘤的研究[J]. 中西医结合学报, 2007,5(6):697-701
[13] Ling CQ, Su YH . Possibility and necessity of constructing new nanoformula systems of traditional Chinese medicine[J]. J Chin Integr Med, 2010,8(2):101-105
凌昌全, 苏永华 . 构建纳米方剂体系的可能性和必要性[J]. 中西医结合学报, 2010,8(2):101-105
[14] Xie GP, Sun J . Pharmacokinetics of nanoparticles in vivo and its influence factors[J]. Kou Qiang Cai Liao Qi Xie, 2010,19(1):23-25, 33
谢广平, 孙皎 . 纳米颗粒的体内药代动力学及其影响因素[J]. 口腔材料器械, 2010,19(1):23-25, 33
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