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Preparation and Enhanced Oral Bioavailability of Cryptotanshinone-Loaded Solid Lipid Nanoparticles

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Abstract

In this study, solid lipid nanoparticles (SLNs) were successfully prepared by an ultrasonic and high-pressure homogenization method to improve the oral bioavailability of the poorly water-soluble drug cryptotanshinone (CTS). The particle size and distribution, drug loading capacity, drug entrapment efficiency, zeta potential, and long-term physical stability of the SLNs were characterized in detail. A pharmacokinetic study was conducted in rats after oral administration of CTS in different SLNs, and it was found that the relative bioavailability of CTS in the SLNs was significantly increased compared with that of a CTS-suspension. The incorporation of CTS in SLNs also markedly changes the metabolism behavior of CTS to tanshinone IIA. These results indicate that CTS absorption is enhanced significantly by employing SLN formulations, and SLNs represent a powerful approach for improving the oral absorption of poorly soluble drugs.

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References

  1. Yang S, Gursoy RN, Lambert G, Benita S. Enhanced oral absorption of paclitaxel in a novel self-microemulsifying drug delivery system with or without concomitant use of P-glycoprotein inhibitors. Pharm Res. 2004;21:261–70.

    Article  CAS  PubMed  Google Scholar 

  2. Itoh K, Matsui S, Tozuka Y, Oguchi T, Yamamoto K. Improvement of physicochemical properties of N-4472. Part II: characterization of N-4472 microemulsion and the enhanced oral absorption. Int J Pharm. 2002;246:75–83.

    Article  CAS  PubMed  Google Scholar 

  3. Brocks DR, Betageri GV. Enhanced oral absorption of halofantrine enantiomers after encapsulation in a proliposomal formulation. J Pharm Pharmacol. 2002;54:1049–53.

    Article  CAS  PubMed  Google Scholar 

  4. Balakrishnan P, Lee BJ, Oh DH, Kim JO, Lee YI, Kim DD et al. Enhanced oral bioavailability of coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm. 2009;374:66–72.

    Article  CAS  PubMed  Google Scholar 

  5. Kennedy M, Hu J, Gao P, Li L, Ali-Reynolds A, Chal B et al. Enhanced bioavailability of a poorly soluble VR1 antagonist using an amorphous solid dispersion approach: a case study. Mol Pharm. 2008;5:981–93.

    Article  CAS  PubMed  Google Scholar 

  6. Chen Y, Lu Y, Chen J, Lai J, Sun J, Hu F et al. Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. Int J Pharm. 2009;376:53–60.

    Article  Google Scholar 

  7. Yang L, Geng Y, Li H, Zhang Y, You J, Chang Y. Enhancement the oral bioavailability of praziquantel by incorporation into solid lipid nanoparticles. Pharmazie. 2009;64:86–9.

    CAS  PubMed  Google Scholar 

  8. Li H, Zhao X, Ma Y, Zhai G, Li L, Lou H. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Release. 2009;133:238–44.

    Article  CAS  PubMed  Google Scholar 

  9. Ugazio E, Cavalli R. Gasco M.R. Incorporation of cyclosporin A in solid lipid nanoparticles (SLN). Int J Pharm. 2002;241:341–4.

    Article  CAS  PubMed  Google Scholar 

  10. Schwarz C, Mehnert W. Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug incorporation and physicochemical characterization. J Microencapsul. 1999;16:205–13.

    Article  CAS  PubMed  Google Scholar 

  11. Manjunath K, Reddy JS, Venkateswarlu V. Solid lipid nanoparticles as drug delivery systems. Methods Find Exp Clin Pharmacol. 2005;27(2):127–44.

    Article  CAS  PubMed  Google Scholar 

  12. Hu L, Tang X, Cui F. Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol. 2004;56:1527–35.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou S, Feng X, Kestell P, Paxton JW, Baguley BC, Chan E. Transport of the investigational anti-cancer drug 5, 6-dimethylxanthenone-4-acetic acid and its acyl glucuronide by human intestinal Caco-2 cells. Eur J Pharm Sci. 2005;24:513–24.

    Article  CAS  PubMed  Google Scholar 

  14. Kang BY, Chung SW, Kim SH, Ryu SY, Kim TS. Inhibition of interleukin-12 and interferon production in immune cells by tanshinones from Salvia miltiorrhiza. Immunopharmacol. 2000;49:355–61.

    Article  CAS  Google Scholar 

  15. Wang AM, Sha SH, Lesniak W, Schacht J. Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo. Antimicrob Agents Chemother. 2003;47:1836–41.

    Article  CAS  PubMed  Google Scholar 

  16. Hur JM, Shim JS, Jung HJ, Kwon HJ. Cryptotanshinone but not tanshinone IIA inhibits angiogenesis in vitro. Exp Mol Med. 2005;37:133–7.

    CAS  PubMed  Google Scholar 

  17. Jin DZ, Yin LL, Ji XQ, Zhu XZ, Zhou S, Feng X et al. Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its expression. Eur J Pharmacol. 2006;549:166–72.

    Article  CAS  PubMed  Google Scholar 

  18. Don MJ, Shen CC, Syu WJ, Ding YH, Sun CM. Cytotoxic and aromatic constituents from Salvia miltiorrhiza. Phytochem. 2006;67:497–503.

    Article  CAS  Google Scholar 

  19. Zhang J, Huang M, Guan S, Bi HC, Pan Y, Duan W et al. A mechanistic study of the intestinal absorption of cryptotanshinone, the major active constituent of Salvia miltiorrhiza. J Pharmacol Exp Ther. 2006;317:1285–94.

    Article  CAS  PubMed  Google Scholar 

  20. Xue M, Cui Y, Wang HQ. Pharmacokinetics of cryptotanshinone and its metabolite in pigs. Acta Pharm Sin. 1999;34:81–4.

    CAS  Google Scholar 

  21. Song M, Hang TJ, Zhang ZX, Du R, Chen J. Determination of cryptotanshinone and its metabolite in rat plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;827:205–9.

    Article  CAS  PubMed  Google Scholar 

  22. Xu Y, Xue F, Jia XN, Zhang YY, Wang JX. The research of extraction parameters of cryptotanshinone from Salvia miltiorrhiza Bunge (danshen). Northwest Pharm J. 2008;23:145–7.

    CAS  Google Scholar 

  23. Hao H, Wang G, Li P, Li J, Ding Z. Simultaneous quantification of cryptotanshinone and its active metabolite tanshinone IIA in plasma by liquid chromatography/tandem mass spectrometry (LC–MS/MS). J Pharm and Biomedical Anal. 2006;40:382–8.

    Article  CAS  Google Scholar 

  24. Wissing SA, Kayser O, Muller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev. 2004;56:1257–72.

    Article  CAS  PubMed  Google Scholar 

  25. Wacher VJ, Salphati L, Benet LZ. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv Drug Deliv Rev. 2001;46:89–102.

    Article  CAS  PubMed  Google Scholar 

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None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.

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Correspondence to LianDong Hu.

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Hu, L., Xing, Q., Meng, J. et al. Preparation and Enhanced Oral Bioavailability of Cryptotanshinone-Loaded Solid Lipid Nanoparticles. AAPS PharmSciTech 11, 582–587 (2010). https://doi.org/10.1208/s12249-010-9410-3

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