积雪草总苷脂质体的制备及体外透皮研究
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摘要
目的优化积雪草总苷(CTG)脂质体的制备工艺,并考察其体外透皮特性规律。方法采用逆相蒸发法,以羟基积雪草苷、积雪草苷的包封率为评价指标,通过单因素考察结合Box-Behnken效应面法优化CTG脂质体的制备工艺,并对其表面特征、包封率、粒径、Zeta电位、体外释放度及体外透皮性能进行考察。结果最佳处方为卵磷脂-胆固醇的质量比4∶1,卵磷脂-CTG的质量比23.22∶1,有机相-水相的体积比7∶1。所得脂质体形态呈球型,表面圆整、无粘连;平均粒径201.7 nm;Zeta电位-15.7 m V;羟基积雪草苷、积雪草苷的平均包封率为75.85%、84.94%;羟基积雪草苷、积雪草苷体外12 h累积释放率分别为52.10%、45.97%;脂质体中羟基积雪草苷、积雪草苷的透皮速率拟合方程分别为Q=67.93 t1/2-50.34,R2=0.988,Q=139.74 t1/2-241.2,R2=0.987;皮肤滞留量分别为76.0、48.7μg/cm2,相对原料药溶液提高到1.56和1.18倍。结论优选的制备工艺合理可行、稳定性好,所得CTG脂质体包封率高、粒径小、皮肤滞留量大、缓释作用明显。
Objective To optimize the preparation technology for Centella asiatica total glucosides(CTG) liposome and to investigate its percutaneous permeability in vitro. Methods Liposomes were prepared by reverse-phase evaporation technique. Taking the entrapment efficiency of madecassoside and asiaticoside as indexes, the preparation of liposome was optimized by using single factor and Box-Behnken response surface method. The properties of liposomes including morphology, entrapment efficiency, mean diameter, Zeta potential, and accumulative release were studied. Results The optimal formulation was lecithin-cholesterol(4∶1), lecithin-CTG(23.22∶1), and organic-aqueous(7∶1). The liposome was smooth and spherieal in appearance, mean diameter, and Zeta potential were 201.7 nm and-15.7 m V, respectively. The entrapment efficiency of madecassoside and asiaticoside were 75.85% and 84.94%. The in vitro 12 h accumulative release was 52.10% and 45.97%. The equations for the permeation rate of madecassoside and asiaticoside in liposomes were Q = 67.93 t1/2-50.34, R2 = 0.988, Q = 139.74 t1/2-241.2, R2 = 0.987, respectively. The retention amount in the skin was 76 μg/cm2 and 48.7 μg/cm2, which were 1.56 and 1.18 times higher than those of solution. Conclusion The optimized process is rational, feasible, and good stability. The CTG liposome prepared in this study have the smaller size, the higher encapsulation efficiency, higher retain in skin and obvious sustained-release effects.
Objective To optimize the preparation technology for Centella asiatica total glucosides(CTG) liposome and to investigate its percutaneous permeability in vitro. Methods Liposomes were prepared by reverse-phase evaporation technique. Taking the entrapment efficiency of madecassoside and asiaticoside as indexes, the preparation of liposome was optimized by using single factor and Box-Behnken response surface method. The properties of liposomes including morphology, entrapment efficiency, mean diameter, Zeta potential, and accumulative release were studied. Results The optimal formulation was lecithin-cholesterol(4∶1), lecithin-CTG(23.22∶1), and organic-aqueous(7∶1). The liposome was smooth and spherieal in appearance, mean diameter, and Zeta potential were 201.7 nm and-15.7 m V, respectively. The entrapment efficiency of madecassoside and asiaticoside were 75.85% and 84.94%. The in vitro 12 h accumulative release was 52.10% and 45.97%. The equations for the permeation rate of madecassoside and asiaticoside in liposomes were Q = 67.93 t1/2-50.34, R2 = 0.988, Q = 139.74 t1/2-241.2, R2 = 0.987, respectively. The retention amount in the skin was 76 μg/cm2 and 48.7 μg/cm2, which were 1.56 and 1.18 times higher than those of solution. Conclusion The optimized process is rational, feasible, and good stability. The CTG liposome prepared in this study have the smaller size, the higher encapsulation efficiency, higher retain in skin and obvious sustained-release effects.
引文
[1]中国药典[S].一部.2015.
[2]张蕾磊,王海生,姚庆强,等.积雪草化学成分研究[J].中草药,2005,36(12):1761-1763.
[3]戴卫波,梅全喜,孔祥廉.积雪草的化学成分与药理作用研究进展[J].时珍国医国药,2009,20(6):1566-1568.
[4]翁小香,黄文武,孔德云.积雪草中三萜类成分及其药理活性研究进展[J].中国医药工业杂志,2011,42(9):710-716.
[5]冯旭,郭飞飞,赵龙,等.积雪草酸药理作用及其结构修饰的研究进展[J].中草药,2014,45(7):1037-1042.
[6]王毅.积雪草苷类化合物对神经系统药理作用研究进展[J].药物评价研究,2016,39(1):136-142.
[7]Wan J,Gong X,Jiang R,et al.Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide-treated rat through up-regulation of heme oxygenase-1[J].Phytother Res Ptr,2013,27(8):1136-1142.
[8]祁少海,谢举临,利天增,等.积雪草甙对烧伤增生性瘢痕作用的实验研究[J].中华烧伤杂志,2000,16(1):53-56.
[9]Liu M,Dai Y,Li Y,et al.Madecassoside isolated from Centella asiatica herbs facilitates burn wound healing in mice[J].Planta Med,2008,74(8):809-815.
[10]薛冰心.影响药物经皮吸收的客观因素[J].中国现代医学杂志,2010,20(16):2479-2483.
[11]翁骏.积雪草苷及其类似物的吸收和代谢性质研究[D].北京:中国人民解放军军事医学科学院,2006.
[12]王佳宇,郭成杰,袁瑞娟,等.积雪草总苷脂质体的肠吸收特征研究[J].中草药,2015,46(10):1487-1492.
[13]彭向前,张鉴.脂质体作为经皮局部给药载体的研究进展[J].中国药事,2005,19(6):358-360.
[14]苏瑾,王丹,胡孟洋,等.山药总多糖脂质体的制备及表征[J].中国实验方剂学杂志,2016,22(16):18-21.
[15]程怡,吴琼,余秋强,等.Box-Behnken效应面法优化多西他赛长循环脂质体处方[J].中草药,2012,43(10):1946-1950.
[16]张丹,廖芳,周洁,等.Box-Behnken Design-响应面优化法优化芍药总苷脂质体的制备工艺及体外释放研究[J].中草药,2015,46(3):359-364.
[17]张传辉,贾成友,李微,等.三七接骨凝胶膏剂的制备及体外透皮特性研究[J].中草药,2015,46(5):654-664.
[18]马伟,尹莉芳,周建平,等.Box-Behnken中心组合设计优化甘草酸二铵缓释片的处方[J].中草药,2008,39(10):1486-1490.
[19]邹节明,周艳林,吴敏菊.HPLC-ELSD法测定三金片和三金胶囊中积雪草苷和羟基积雪草苷的含量[J].药物分析杂志,2005,25(10):1250-1252.
[2]张蕾磊,王海生,姚庆强,等.积雪草化学成分研究[J].中草药,2005,36(12):1761-1763.
[3]戴卫波,梅全喜,孔祥廉.积雪草的化学成分与药理作用研究进展[J].时珍国医国药,2009,20(6):1566-1568.
[4]翁小香,黄文武,孔德云.积雪草中三萜类成分及其药理活性研究进展[J].中国医药工业杂志,2011,42(9):710-716.
[5]冯旭,郭飞飞,赵龙,等.积雪草酸药理作用及其结构修饰的研究进展[J].中草药,2014,45(7):1037-1042.
[6]王毅.积雪草苷类化合物对神经系统药理作用研究进展[J].药物评价研究,2016,39(1):136-142.
[7]Wan J,Gong X,Jiang R,et al.Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide-treated rat through up-regulation of heme oxygenase-1[J].Phytother Res Ptr,2013,27(8):1136-1142.
[8]祁少海,谢举临,利天增,等.积雪草甙对烧伤增生性瘢痕作用的实验研究[J].中华烧伤杂志,2000,16(1):53-56.
[9]Liu M,Dai Y,Li Y,et al.Madecassoside isolated from Centella asiatica herbs facilitates burn wound healing in mice[J].Planta Med,2008,74(8):809-815.
[10]薛冰心.影响药物经皮吸收的客观因素[J].中国现代医学杂志,2010,20(16):2479-2483.
[11]翁骏.积雪草苷及其类似物的吸收和代谢性质研究[D].北京:中国人民解放军军事医学科学院,2006.
[12]王佳宇,郭成杰,袁瑞娟,等.积雪草总苷脂质体的肠吸收特征研究[J].中草药,2015,46(10):1487-1492.
[13]彭向前,张鉴.脂质体作为经皮局部给药载体的研究进展[J].中国药事,2005,19(6):358-360.
[14]苏瑾,王丹,胡孟洋,等.山药总多糖脂质体的制备及表征[J].中国实验方剂学杂志,2016,22(16):18-21.
[15]程怡,吴琼,余秋强,等.Box-Behnken效应面法优化多西他赛长循环脂质体处方[J].中草药,2012,43(10):1946-1950.
[16]张丹,廖芳,周洁,等.Box-Behnken Design-响应面优化法优化芍药总苷脂质体的制备工艺及体外释放研究[J].中草药,2015,46(3):359-364.
[17]张传辉,贾成友,李微,等.三七接骨凝胶膏剂的制备及体外透皮特性研究[J].中草药,2015,46(5):654-664.
[18]马伟,尹莉芳,周建平,等.Box-Behnken中心组合设计优化甘草酸二铵缓释片的处方[J].中草药,2008,39(10):1486-1490.
[19]邹节明,周艳林,吴敏菊.HPLC-ELSD法测定三金片和三金胶囊中积雪草苷和羟基积雪草苷的含量[J].药物分析杂志,2005,25(10):1250-1252.