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Antitumor activity and pharmacokinetics of podophyllotoxin incorporated into solid lipid nanoparticles

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Abstract

To evaluate the antitumor activity and pharmacokinetics of podophyllotoxin (PPT) incorporated into solid lipid nanoparticles (SLN), Kunming mice inoculated with flesh tumor were used as animal model. The mice received a single daily intraperitoneal injection of PPT in 20% ethanol (5 mg/kg) and PPT-SLN (5 mg/kg in PPT) for 3 weeks. Gross tumor volumes, body weight and clinical observations were recorded daily. The mice were sacrificed for 24 h after the last administration, and the tumor inhibition rate was calculated with the tumor weight. For the pharmacokinetics research, the mice were treated with intraperitoneal injection of PPT (10 mg/kg) and PPT-SLN (10 mg/kg in PPT). Blood samples were collected at different time to determine the PPT concentration in plasma by HPLC. Blood drug level-time curve was made and pharmacokinetic parameters were calculated. As a result of drug administration, the tumor volume and weight of the mice injected with PPT-SLN were significantly restrained compared with mice treated with PPT or negative control. The tumor inhibition rate of 58.13% showed a significant antitumor activity of PPT-SLN. At the same time, the increased weight gain of the mice injected with PPT-SLN suggested a reduced toxicity of PPT in SLN. Pharmacokinetics study displayed a higher blood concentration, a prolonged circulation time, and an increased bioavailability of PPT-SLN compared with those of PPT. Our results demonstrated that PPT-SLN could optimize pharmacokinetics, enhance antitumor activity and attenuate toxicity, so it has a promising prospect for the application in anti-tumor treatment.

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References

  1. Kaplan I W. Codylomata acuminata. New Orleans Med Surg J, 1942, 388

  2. Wallin K L, Wiklund F, Angstrom T, Bergman F, Stendahl U, Wadell G, Hallmans G, Dillner J. Type-specific persistence of human papillomavirus DNA before the development of invasive cervical cancer. N Engl J Med, 1999, 341(22): 1633–1638

    Article  CAS  Google Scholar 

  3. Sand P C, Weisaman K, Quercetin and kaempherol. An argument against the use of podophyllin. Genitourin Med, 1995, 71(1): 92–93

    Google Scholar 

  4. Yu P F, Chen H, Wang J, He C X, Cao B, Li M, Yang N, Lei Z Y, Cheng M S. Design, synthesis cytotoxicity of novel podophyllotoxin derivatives. Chem Pharm Bull, 2008, 56(6): 831–834

    Article  CAS  Google Scholar 

  5. Reddy P B, Paul D V, Agrawal S K, Saxena A K, Kumar H M, Qazi G N. Design, synthesis, and biological testing of 4beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin analogues as antitumor agents. Arch Pharm (Weinheim), 2008, 341(2): 126–131

    Article  CAS  Google Scholar 

  6. Wang S L, Sun X Y, Zhang C J, Wang M, Li W Z, Liu S H, Ni Y M, Yao S D. Antitumor mechanism of VP-16: A pulse radiolysis study. Sci China Ser B-Chem, 2002, 45(4): 394–397

    Article  CAS  Google Scholar 

  7. Sun X Y, Zhang C J, Wang M, Wang S L, Ni Y M, Yao S D. Laser flash photolysis and pulse radiolysis study on chemical activity of VP-16 and podophyllotoxin. Sci China Ser B-Chem, 2002, 45(2): 191–199

    Article  CAS  Google Scholar 

  8. Wang S L. Oxidizing mechanism of podophyllotoxin and its derivatives by sodium persulfate. Sci China Ser B-Chem, 1996, 39(4): 425–425

    CAS  Google Scholar 

  9. Zhu R R, Wang SL, Sun X Y, Zhang R, Yao S D. The protection effect of β-CD on DNA damage induced by ultrafine TiO2. Sci China Ser B-Chem, 2007, 50(2): 272–275

    Article  CAS  Google Scholar 

  10. Li S Q, Zhu H, Zhu R R, Sun X Y, Yao S D, Wang S L. Impact and mechanism of TiO2 nanoparticles on DNA synthesis in vitro. Sci China Ser B-Chem, 2008, 51(4): 367–372

    Article  CAS  Google Scholar 

  11. Xue Y H, Zhang R, Sun X Y, Wang S L. The construction and characterization of layered double hydroxides as delivery vehicles for podophyllotoxins. J Mater Sci: Mater Med, 2008, 19(3): 1197–1202

    Article  CAS  Google Scholar 

  12. Zhu H, Xu J Z, Li S Q, Sun X Y, Yao S D, Wang S L. Effects of high-energy-pulse-electron beam radiation on biomacromolecules. Sci China Ser B-Chem, 2008, 51(1): 86–91

    Article  CAS  Google Scholar 

  13. Qin L L, Wang S L, Zhang R, Zhu R R, Sun X Y, Yao S D. Two different approaches to synthesizing Mg-Al-layered double hydroxides as folic acid carriers. J Phys Chem Solids, 2008, 69(11): 2779–2784

    Article  CAS  Google Scholar 

  14. Zhao P, Wang M, Zhang S P, Shao S C, Sun X Y, Yao S D, Wang S L. Photochemical properties of a new kind of anti-cancer drug: N-glycoside compound. Sci China Ser B-Chem, 2008, 51(9): 872–877

    Article  CAS  Google Scholar 

  15. Vyas S P, Rai, S, Paliwal R, Gupta P N, Khatri K, Goyal A, Vaidya B. Solid lipid nanoparticles (SLNs) as a rising tool in drug delivery science: One step up in nanotechnology. Curr Nanosci, 2008, 4(1): 30–44

    Article  Google Scholar 

  16. Wang S L, Sun X Y, Zhang R, Nie Q, Yao S D. Chin Patent, CN200510111606.3

  17. Zhang X Y, Ni J M, Qiao H. Study on antitumor effects of podophyllotoxin nanoliposome. Chin J Chin Mater Med (in Chinese), 2006, 31(2): 148–150

    CAS  Google Scholar 

  18. Sawant K, Dodiya S. Recent advances and patents on solid lipid nanoparticles. Recent Patents Drug Deliv Formul, 2008, 2(2): 120–135

    Article  CAS  Google Scholar 

  19. Elisabetta E, Martina F, Matteo M, Markus D, Lydia P, Paolo M, Elisa S, Francesco L, Enea M, Michele M, Rita C. Solid Lipid nanoparticles as delivery systems for bromocriptine. Pharm Res, 2008, 25(7): 1521–1530

    Article  CAS  Google Scholar 

  20. Gasco M. Lipid nanoparticles: Perspectives and challenges. Adv Drug Deliver Rev, 2007, 59(6): 377–378

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Life Science and Technology, Tongji University, Shanghai, 200092, China

    Meng Xue, RongRong Zhu, LiLi Qin, FaJie Li, ZhiXue Liu, XiaoYu Sun & ShiLong Wang

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  1. Meng Xue
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  2. RongRong Zhu
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  3. LiLi Qin
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  4. FaJie Li
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  5. ZhiXue Liu
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  6. XiaoYu Sun
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  7. ShiLong Wang
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Correspondence to ShiLong Wang.

Additional information

Supported by the National Natural Science Foundation of China (Grant No. 50673078), the Innovation Program of Shanghai Municipal Education Commission (Grant No. 08ZZ21) and the Shanghai Key Fundamental Project (Grant No. 07DZ19603)

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Xue, M., Zhu, R., Qin, L. et al. Antitumor activity and pharmacokinetics of podophyllotoxin incorporated into solid lipid nanoparticles. Sci. China Ser. B-Chem. 52, 1253–1257 (2009). https://doi.org/10.1007/s11426-009-0035-x

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  • DOI: https://doi.org/10.1007/s11426-009-0035-x

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