处方组成对槲皮素传递体透皮作用的影响
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摘要
采用注入法-高压均质法制备槲皮素(1)传递体。采用改良Franz扩散池法,考察不同表面活性剂(Tween-80、胆酸钠、癸酸钠及油酸钠)、氯化钠及磷脂种类对传递体中1的累积渗透量及皮肤滞留量的影响。其中,采用蛋黄卵磷脂以及Tween-80、胆酸钠、癸酸钠或油酸钠制备的1传递体,24 h累积渗透量分别为(9.37±2.59)、(8.73±1.34)、(6.79±1.83)和(3.46±0.66)mg/cm~2;皮肤滞留量为0.97~1.34mg/cm~2。与1混悬剂组[24 h累积渗透量为0,皮肤滞留量为(0.11±0.06)mg/cm~2]相比,传递体中1的透皮能力和皮肤滞留量显著提高(P<0.05);与油酸钠组相比,Tween-80组和胆酸钠组存在显著差异(P<0.05)。含Tween-80的传递体中加入氯化钠或用大豆磷脂替换蛋黄卵磷脂后,1的24 h累积渗透量增加至(13.03±4.15)或(10.58±6.98)mg/cm~2,但均没有显著差异(P>0.05)。结果显示,以Tween-80及大豆磷脂为材料,不加入氯化钠制备的1传递体z电位为(-38.0±1.5)mV,并显著提高了1的皮肤渗透性及滞留量。
The quercetin(1) transfersomes were prepared by injection and high-pressure homogenization method.The effects of surfactants(Tween-80,sodium cholate,sodium decanoate and sodium oleate),sodium chloride and phospholipids used in the transfersome formulations on the cumulative permeation amount and skin retention of 1 were evaluated by the modified Franz diffusion cell method.The cumulative permeation amount of 1 transfersomes containing egg-yolk phosphatidylcholine(EPC) and Tween-80,sodium cholate,sodium decanoate or sodium oleate were(9.37±2.59),(8.73±1.34),(6.79±1.83) and(3.46±0.66)mg/cm~2,respectively.And the retention amounts in skin of the above groups were in the range of 0.97—1.34 μg/cm~2.Compared wiht 1 suspension,whose cumulative permeation amount at 24 h and skin retention were 0 and(0.11±0.06)mg/cm~2,the permeation ability and skin retention of 1 transfersomes were significantly increased(P<0.05).Moreover,the cumulative permeation amounts of the transfersomes containing Tween-80 or sodium cholate were significantly higher than that of the transfersomes containing sodium oleate(P<0.05).Adding sodium chloride into the transfersomes containing Tween-80 or using soybean phosphatidylcholine(SPC) instead of EPC,the cumulative permeation amounts were increased to(13.03±4.15) or(10.58±6.98)mg/cm~2,but there was no obvious differences were observed(P>0.05).The results showed that owing to its low z potential,transfersomes prepared by Tween-80(especially that containing sodium chloride) showed a higher transdermal property and better affinity to the skin,whose p H value of the formulation was close to that of normal people,compared with vesicles prepared by other anionic surfactants(sodium cholate,sodium decanoate or sodium oleate).In summary,the 1 transfersomes with Tween-80 and SPC and without Na Cl led to high z potential [(-38.0±1.5)mV] and remarkable enhances of the cumulative permeation and retention amount of 1.
The quercetin(1) transfersomes were prepared by injection and high-pressure homogenization method.The effects of surfactants(Tween-80,sodium cholate,sodium decanoate and sodium oleate),sodium chloride and phospholipids used in the transfersome formulations on the cumulative permeation amount and skin retention of 1 were evaluated by the modified Franz diffusion cell method.The cumulative permeation amount of 1 transfersomes containing egg-yolk phosphatidylcholine(EPC) and Tween-80,sodium cholate,sodium decanoate or sodium oleate were(9.37±2.59),(8.73±1.34),(6.79±1.83) and(3.46±0.66)mg/cm~2,respectively.And the retention amounts in skin of the above groups were in the range of 0.97—1.34 μg/cm~2.Compared wiht 1 suspension,whose cumulative permeation amount at 24 h and skin retention were 0 and(0.11±0.06)mg/cm~2,the permeation ability and skin retention of 1 transfersomes were significantly increased(P<0.05).Moreover,the cumulative permeation amounts of the transfersomes containing Tween-80 or sodium cholate were significantly higher than that of the transfersomes containing sodium oleate(P<0.05).Adding sodium chloride into the transfersomes containing Tween-80 or using soybean phosphatidylcholine(SPC) instead of EPC,the cumulative permeation amounts were increased to(13.03±4.15) or(10.58±6.98)mg/cm~2,but there was no obvious differences were observed(P>0.05).The results showed that owing to its low z potential,transfersomes prepared by Tween-80(especially that containing sodium chloride) showed a higher transdermal property and better affinity to the skin,whose p H value of the formulation was close to that of normal people,compared with vesicles prepared by other anionic surfactants(sodium cholate,sodium decanoate or sodium oleate).In summary,the 1 transfersomes with Tween-80 and SPC and without Na Cl led to high z potential [(-38.0±1.5)mV] and remarkable enhances of the cumulative permeation and retention amount of 1.
引文
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[8]马云淑,赵浩如,林以宁.葛根素及其磷脂复合物的体外透皮实验研究[J].中国中药杂志,2000,25(5):274-276.
[9]Rojanasakul Y,Wang LY,Bhat M,et al.The transport barrier of epithelia:A comparative study on membrane permeability and charge selectivity in the rabbit[J].Pharm Res,1992,9(8):1029-1034.
[10]Liu D,Hu H,Lin Z,et al.Quercetin deformable liposome:Preparation and effi cacy against ultraviolet B induced skin damages in vitro and in vivo[J].J Photochem Photobiol B,2013,127:8-17.
[11]Anderberg EK,Lindmark T,Artursson P.Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route[J].Pharm Res,1993,10(6):857-864.
[12]Wachter C,Vierl U,Cevc G.Adaptability and elasticity of the mixed lipid bilayer vesicles containing non-ionic surfactant designed for targeted drug delivery across the skin[J].JDrug Target,2008,16(7-8):611-625.
[13]徐辉碧,杨祥良,谢长生,等.纳米技术在中药研究中的应用[J].中国药科大学学报,2001,32(3):161-165.
[2]D'Andrea G.Quercetin:A flavonol with multifaceted therapeutic applications?[J].Fitoterapia,2015,106:256-271.
[3]廖瀚,甄宇红,丁超,等.槲皮素的生物活性机制及药动学特点[J].现代生物医学进展,2012,12(16):3174-3177.
[4]杨晓春,张强,吴镭.目前我国透皮给药系统研究的基本思路[J].中国新药杂志,2001,10(5):321-324.
[5]Cevc G.Lipid vesicles and other colloids as drug carriers on the skin[J].Adv Drug Deliv Rev,2004,56(5):675-711.
[6]华晓东,任变文.经皮给药系统的研究进展[J].现代药物与临床,2009,24(5):282-285.
[7]郑立强,沈强,徐桂英,等.非离子性糖脂质囊泡的稳定性研究(英文)[J].日用化学品科学,2000,23(S2):1-7.
[8]马云淑,赵浩如,林以宁.葛根素及其磷脂复合物的体外透皮实验研究[J].中国中药杂志,2000,25(5):274-276.
[9]Rojanasakul Y,Wang LY,Bhat M,et al.The transport barrier of epithelia:A comparative study on membrane permeability and charge selectivity in the rabbit[J].Pharm Res,1992,9(8):1029-1034.
[10]Liu D,Hu H,Lin Z,et al.Quercetin deformable liposome:Preparation and effi cacy against ultraviolet B induced skin damages in vitro and in vivo[J].J Photochem Photobiol B,2013,127:8-17.
[11]Anderberg EK,Lindmark T,Artursson P.Sodium caprate elicits dilatations in human intestinal tight junctions and enhances drug absorption by the paracellular route[J].Pharm Res,1993,10(6):857-864.
[12]Wachter C,Vierl U,Cevc G.Adaptability and elasticity of the mixed lipid bilayer vesicles containing non-ionic surfactant designed for targeted drug delivery across the skin[J].JDrug Target,2008,16(7-8):611-625.
[13]徐辉碧,杨祥良,谢长生,等.纳米技术在中药研究中的应用[J].中国药科大学学报,2001,32(3):161-165.