Skip to main content
SpringerLink
Log in

Preparation, Safety, Pharmacokinetics, and Pharmacodynamics of Liposomes Containing Brucea javanica Oil

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Brucea javanica oil-loaded liposomes (BJOL) were prepared through thin film hydration method and characterized by transmission electron microscope, dynamic light scattering, and differential scanning calorimetry. Acute toxicity of B. javanica oil (BJO) in liposomes was assessed by determining the number of deaths of Kunming mice over intravenous treatment for 2 weeks. The pharmacokinetic behavior of the main active component (oleic acid) was studied in SD rats. The pharmacodynamics of BJOL was investigated using MMC-7721 cell lines and mice with Lewis lung cancer. The commercial emulsion of BJO (BJOE) was used as a reference. The data showed that BJOL had an average diameter of 108.2 nm with a zeta potential of −57.0 mV, drug loading of 3.60%, and entrapment efficiency of 92.40%. The area under curve of BJO in liposomes and emulsions were 2.31 and 1.15 mg min/ml, respectively. Compared with BJOE, mean residence time and elimination half-time (t 1/2) increased 2.8- and 4.0-fold, respectively, and the clearance (CL) decreased 0.5-fold. In the acute toxicity test, the median lethal dose (LD50) of BJOE was 7.35 g/kg. In contrast, all mice treated with liposomes survived even at the highest dosage (12.70 g/kg). The IC50 value of BJOL group was one third of that of BJOE group (p < 0.01), and a less weight loss was observed in the BJOL-treated animals (p < 0.05). In conclusion, the present study suggests that BJOL significantly decreased toxicity of BJO and enhance the antitumor activity. Therefore, liposomes may be a potential effective delivery vehicle for this lipophilic antitumor drug.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bi YL. Quality analysis of Brucea javanica oil. J Zhengzhou Inst Technol. 2001;22(4):72–4.

    Google Scholar 

  2. Wang F, Cao Y, Liu HY, Fu ZD, Han R. Experimental studies on the apoptosis of HL-60 cells induced by Brucea javanica oil emulsion. Zhongguo Zhong Yao Za Zhi. 2003;28(8):759–61.

    PubMed  Google Scholar 

  3. Tang T, Meng LH, Chen LJ, Ding J. Reversal of multidrug resistance and inhibition of DNA topoisomerase by emulsion of seed oil of Brucea. Chin Pharmacol Bull. 2001;17(5):534–9.

    CAS  Google Scholar 

  4. Tan HY, Li Y, Zhu SJ, Wan DG, Cui HJ, Jia LQ, et al. The treatment of 25 cases of elderly patients with advanced non-small cell lung cancer using gemcitabine combined with Brucea joint oil emulsion treatment. China tumor. 2007;16(6):474–5.

    Google Scholar 

  5. Li XG, Nan XY, Dang JG, Li X, Yang SY. An experimental study of effect of Brucea javanica oil emulsion on human renal carcinoma. J Clin Urol. 1998;13(2):82–4.

    Google Scholar 

  6. Nan XY, He DL, Dang JG, Zhang Y, Wang MZ, Yang ZS. Treatment of prostatic carcinoma (Stage C to D) with fructus bruceae emulsion. J Clin Urol. 1998;13(12):531–3.

    Google Scholar 

  7. Xiang Q, Zhou LL, Zhang H, Zhang HB, Yao CS, Hang YD. The pharmacokinetic studies of Brucea javanica oil microemulsions in rats. J Chin Med Mater. 2007;30(9):1113–5.

    CAS  Google Scholar 

  8. Ji XY. One cases of anaphylactic response induced by Brucea javanica oil emulsion injection. J Mod Oncol. 2009;17(8):1537.

    Google Scholar 

  9. Allen TM, Hansen CB, Meneze DE. Pharmacokinetics of long-circulating liposomes. Adv Drug Deliv Rev. 1995;16:267–84.

    Article  CAS  Google Scholar 

  10. Chiu GN, Bally MB, Mayer LD. Targeting of antibody conjugated, phosphatidylserine-containing liposomes to vascular cell adhesion molecule 1 for controlled thrombogenesis. Biochim Biophys Acta. 2003;1613:115–21.

    Article  CAS  PubMed  Google Scholar 

  11. Vemuri S, Rhodes CT. Preparation and characterization of liposomes as therapeutic delivery systems: a review. Pharmaceutics Acta Helvetiae. 1995;70:95–111.

    Article  CAS  Google Scholar 

  12. Yu YL, Lu Y, Tang X, Cui FD. Formulation, preparation and evaluation of an intravenous emulsion containing Brucea javanica oil and Coix seed oil for anti-tumor application. Biol Pharm Bull. 2008;31(4):673–80.

    Article  CAS  PubMed  Google Scholar 

  13. Mehta A, Oeser AM, Carlson MG. Rapid quantitation of free fatty acids in human plasma by high-performance liquid chromatography. J Chromatogr B. 1998;719:9–23.

    Article  CAS  Google Scholar 

  14. Li H, Yue CL, Xiang Q, Yao CS, Zhou LL. Determination of fatty acids in Brucea jananica oil injection by high-performance liquid chromatography. Chin J Mod Appl Pharm. 2006;23(4):329–31.

    CAS  Google Scholar 

  15. Weinkove C, Reed P, Abushufa R. Fatty acids in erythocytes measured by isocratic HPLC. Clin Chem. 1994;40(9):1707–12.

    PubMed  Google Scholar 

  16. Dayan N, Touitou E. Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials. 2000;21:1879–85.

    Article  CAS  PubMed  Google Scholar 

  17. Gao XL, Ji XM. Determining the trap efficiency of liposome using sephadex column chromatography. China Pharm J. 2003;38(7):515–7.

    CAS  Google Scholar 

  18. Li QX, Wang H, Xiao QQ, Kong R. The evaluation and calculation of median lethal dose (LD50) using Bliss method. J Math Med. 1995;4:318–20.

    Google Scholar 

  19. Tian G, Yu JP, Luo HS, Yu BP, Yue H, Li JY. Effect of nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721 cells. World J Gastroenterol. 2002;8(3):483–7.

    CAS  PubMed  Google Scholar 

  20. Sargent JM, Taylor CG. Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia. Brit J Cancer. 1989;60(2):206–10.

    CAS  PubMed  Google Scholar 

  21. Barba I, Cabanas ME, Arus C. The relationship between nuclear magnetic resonance-visible lipids, lipid droplets, and cell proliferation in cultured C6 cells. Cancer Res. 1999;59(8):1861–8.

    CAS  PubMed  Google Scholar 

  22. Takeuchi H, Kojima H, Toyoda T, Yamamoto H, Hino T, Kawashima Y. Prolonged circulation time of doxorubicin-loaded liposomes coated with a modified polyvinyl alcohol after intravenous injection in rats. Eur J Pharm Biopharm. 1999;48:123–9.

    Article  CAS  PubMed  Google Scholar 

  23. Nagayas A, Uchiyama K, Kiwada H. The size of liposomes: a factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs. Adv Drug Deliv Rev. 1999;40:75–87.

    Article  Google Scholar 

  24. Torchilin VP. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annu Rev Biomed Eng. 2006;8:343–75.

    Article  CAS  PubMed  Google Scholar 

  25. Zhu JB, Wen N, Xiong F, Xiong F. Stability and pharmacokinetic studies of O-palmitoyl amylopectin anchored dipyridamole liposomes. Int J Pharm. 2006;313:136–43.

    Article  PubMed  Google Scholar 

  26. Nam NH, Kim Y, You YJ, Hong DH, Kim HM, Ahn BZ. Combretoxazolones: synthesis, cytotoxicity and antitumor activity. Bioorg Med Chem Lett. 2001;11(23):3073–6.

    Article  CAS  PubMed  Google Scholar 

  27. Chang CC, Liu DZ, Lin SY, Liang HJ, Hou WC, Huang WJ, et al. Liposome encapsulation reduces cantharidin toxicity. Food Chem Toxicol. 2008;46:3116–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is financially supported by the major project of National Science and Technology of China for new drugs development (No. 2009ZX09310-004) and “The Six Major Talent” peak project in Jiangsu Province, China (No. 07-C-013).

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China

    Yanxia Cui, Xiaoxu Liu, Rui Ni, Lulu Ma & Jianping Liu

  2. School of Pharmacy, University of Auckland, Auckland, New Zealand

    Zimei Wu

  3. Department of Pharmacology, Nanjing University of Traditional Chinese Medicine, Nanjing, People’s Republic of China

    Xuanxuan Zhu

Authors
  1. Yanxia Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zimei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoxu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rui Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuanxuan Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lulu Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jianping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianping Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cui, Y., Wu, Z., Liu, X. et al. Preparation, Safety, Pharmacokinetics, and Pharmacodynamics of Liposomes Containing Brucea javanica Oil. AAPS PharmSciTech 11, 878–884 (2010). https://doi.org/10.1208/s12249-010-9454-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-010-9454-4

KEY WORDS

Search

Navigation