Abstract
Aim:
To evaluate a mixed micellar drug delivery system composed of sodium cholate and phospholipid for oral administration of silybin, a promising hepatoprotectants.
Methods:
The optimum formulation of sodium cholate/phospholipid-mixed micelles containing silybin was obtained based on the study of pseudo-ternary phase diagram. The dissolution of silybin-mixed micelles was investigated. The pharmacokinetic characteristics and bioavailability after oral administration of silybin-mixed micelles and silybin-N-methylglucamine were compared in dogs.
Results:
The mean particle size of prepared mixed micelles was 75.9±4.2 nm. The largest solubility of silybin was found to be 10.0±1.1 mg/mL in the optimum formulation of mixed micelles. The silybin-sodium cholate/phospholipid-mixed micelles showed a very slow release of silybin 17.5% (w/w) within 72 h in phosphate buffer (pH 7.4) and 15.6% (w/w) in HCl solution (pH 1.2). After oral administration to dogs, the relative bioavailability of mixed micelles versus silybin-N-methylglucamine in dogs was 252.0%.
Conclusion:
Sodium cholate/phospholipid-mixed micelles are promising carriers in orally delivery of silybin, considering their capability of enhancing bioavailability and large-scale production.
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References
Sallee VL, Dietschy JM . Determinants of intestinal mucosal uptake of medium-chain fatty acids and alcohols. J Lipid Res 1973; 14: 475–84.
Westergaard H, Dietschy JM . The mechanism whereby bile acid micelles increase the rate of fatty acid and cholesterol uptake into the intestinal mucosal cell. J Clin Invest 1976; 58: 97–108.
Wilson, FA . Intestinal transport of bile acids. Am J Physiol 1981; 241: G83–G92.
O'Reilly JR, Corrigan OI, O'Driscoll CM . The effect of mixed micellar systems, bile acid/fatty acids, on the solubility and intestinal absorption of clofazimine (B663) in the anesthetized rat. Int J Pharm 1994; 109: 147–94.
Garidel P, Hildebrand A, Blume A . Membranolytic activity of bile salts: Influence of biological membrane properties and composition. Molecules 2007; 12: 2292–326.
Dangi JS, Vyas SP, Dixit VK . Effect of various lipid-bile salt mixed micelles on transfer of amphotericin-B across the everted rat intestine. Drug Dev Ind Pharm 1995; 21: 2021–7.
Wiedmann TS, Kamel L . Examination of the solubilization of drugs by bile salt micelles. J Pharm Sci 2002; 91: 1743–64.
Wiedmann TS, Liang W, Kamel L . Solubilization of drugs by physiological mixtures of bile salts. Pharm Res 2002; 19: 1203–8.
Hammad MA, Müller BW . Increasing drug solubility by means of bile salt-phosphatidylcholine-based mixed micelles. Eur J Pharm Biopharm 1998; 46: 361–7.
Dongowski G, Fritzsch B, Giessler J, Härtl A, Kuhlmann O, Neubert RHH . The influence of bile salts and mixed micelles on the pharmacokinetics of quinine in rabbits. Eur J Pharm Biopharm 2005; 60: 147–51.
Hammad MA, Müller BW . Solubility and stability of lorazepam in bile salt/soya phosphatidylcholine-mixed micelles. Drug Dev Ind Pharm 1999; 25: 409–17.
Guo J, Wu T, Ping Q, Chen Y, Shen J, Jiang G . Solubilization and pharmacokinetic behaviors of sodium cholate/lecithin-mixed micelles containing cyclosporine A. Drug Deliv 2005; 12: 35–9.
Risovic V, Boyd M, Choo E, Wasan KM . Effects of lipid-based oral formulations on plasma and tissue amphotericin B concentrations and renal toxicity in male rats. Antimicrob Agents Chemother 2008; 47: 3339–42.
Chamulitrat W, Burhenne J, Stremmel W . Cytoprotective functions of a bile salt-phospholipid conjugate lysophosphatidyl-ethanolamino-ursodeoxycholate: implications for treatment of liver diseases. J Hepatol 2007; 46: S287.
Chamulitrat W, Burhenne J, Rehlen T, Pathil-Warth A, Stremmel W . A novel bile salt-phospholipid conjugate ursodeoxycholyl-lysophosphatidylethanolamide as a hepatic cytoprotective agent. J Hepatol 2008; 48: S59.
Chamulitrat W, Burhenne J, Rehlen T, Pathil A, Stremmel W . Bile salt-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide as a hepatoprotective agent. Hepatology 2009; 50: 143–54.
Li X, Pei Y, Huang Y, Zhou Y, Zhang Y . Liu Y . In vitro and in vivo evaluation of a selfmicroemulsifying drug delivery system for silybin. J Chin Pharm Sci 2009; 18: 342–7.
Liu X, Sun Y, Zhang Y, Tang X . Preparation and in vitro-in vivo evaluation of silybin lipid microspheres. Asian J Pharm Sci 2007; 2: 204–10.
Xiao Y, Song Y, Chen Z, Ping Q . The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm 2006; 307: 77–82.
Jia LJ, Zhang DR, Li ZY, Feng FF, Wang YC, Dai WT, et al. Preparation and characterization of silybin-loaded nanostructured lipid carriers. Drug Deliv 2010; 17: 11–8.
Li F, Hu J, Jiang Y . Preparation and characterization of solid dispersions of silymarin with polyethylene glycol 6000. J Chin Pharm Sci 2003; 12: 76–81.
Wu W, Wang Y, Que L . Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur J Pharm Biopharm 2006; 63: 288–94.
Acknowledgements
This project was supported by the National Natural Science Foundation of China (Grant No 30472098) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.
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Yu, Jn., Zhu, Y., Wang, L. et al. Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacol Sin 31, 759–764 (2010). https://doi.org/10.1038/aps.2010.55
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DOI: https://doi.org/10.1038/aps.2010.55
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