白花丹醌传递体凝胶的制备及其体外透皮研究
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摘要
目的制备白花丹醌传递体(PBG-T)凝胶,考察其经皮给药的渗透特性。方法采用薄膜-超声分散法制备PBG-T,通过星点设计-效应面法优化PBG-T处方,通过正交试验优化PBG-T凝胶的处方;垂直式Franz扩散池考察PBG-T凝胶体外透皮扩散效果。结果 PBG-T的最优处方工艺为白花丹醌(PBG)10.0 mg,磷脂700.0 mg,聚山梨酯-80 91.5 mg,超声时间13 min;PBG-T凝胶的最优处方为卡波姆1%,甘油5%;以最优处方制得的PBG-T的包封率为(79.88±2.26)%,平均粒径为(125.64±4.54)nm,Zeta电位为(-30.97±1.13)m V;PBG-T凝胶12 h的累积渗透率为70.0%。结论 PBG-T凝胶的处方工艺稳定、可行,且可以减缓PBG的体外释放,增加其累积渗透率。
Objective To prepare plumbagin transfersomal(PBG-T) gel and investigate its transdermal penetration characteristics in vitro. Methods Plumbagin transfersomes were prepared by film-ultrasonic dispersion method. The optimal prescription condition of PBG-T was selected by central composite design and response surface method. The formula of PBG-T gel was optimized by orthogonal test. The Franz diffusion cell was used to investigate transdermal penetration characteristics of PBG-T gel in vitro. Results The optimal prescription condition of transfersomes was determined as drug 10.0 mg, phospholipids 700.0 mg, Tween-80 91.5 mg, ultrasonication time 13 min. The optimal prescription condition of transfersomal gel was 1% carbomer 940 as gel matrix, and 5% glycerol as the humectant. According to the optimized prescription, the entrapment efficiency, the mean particle size, and Zeta potential of PBG-T were(79.88 ± 2.26)%,(125.64 ± 4.54) nm, and(-30.97 ± 1.13) m V. The cumulative penetration rate of PBG-T gel was 70.0% at 12 h. Conclusion The optimal preparation technique is stable and feasible. Transfersomal gel features a sustained release in vitro, the transfersomal gel can increase penetration rate of plumbagin through the skin of rats.
Objective To prepare plumbagin transfersomal(PBG-T) gel and investigate its transdermal penetration characteristics in vitro. Methods Plumbagin transfersomes were prepared by film-ultrasonic dispersion method. The optimal prescription condition of PBG-T was selected by central composite design and response surface method. The formula of PBG-T gel was optimized by orthogonal test. The Franz diffusion cell was used to investigate transdermal penetration characteristics of PBG-T gel in vitro. Results The optimal prescription condition of transfersomes was determined as drug 10.0 mg, phospholipids 700.0 mg, Tween-80 91.5 mg, ultrasonication time 13 min. The optimal prescription condition of transfersomal gel was 1% carbomer 940 as gel matrix, and 5% glycerol as the humectant. According to the optimized prescription, the entrapment efficiency, the mean particle size, and Zeta potential of PBG-T were(79.88 ± 2.26)%,(125.64 ± 4.54) nm, and(-30.97 ± 1.13) m V. The cumulative penetration rate of PBG-T gel was 70.0% at 12 h. Conclusion The optimal preparation technique is stable and feasible. Transfersomal gel features a sustained release in vitro, the transfersomal gel can increase penetration rate of plumbagin through the skin of rats.
引文
[1]谭明雄,王恒山,陈振锋,等.白花丹化学成分和药理活性研究进展[J].中草药,2007,38(2):289-293.
[2]中华人民共和国卫生部药材标准·维吾尔药分册[S].1999.
[3]云南省中药材标准·第四册[S].2005.
[4]广西中药材标准·第四册[S].1992.
[5]韦燕飞,李景强,张志伟,等.白花丹醌对瘦素刺激的人肝星状细胞周期及其相关蛋白表达的影响[J].中草药,2012,43(9):1776-1780.
[6]史岑慧.白花丹治疗类风湿性关节炎的实验研究[D].广州:广东中医药大学,2013.
[7]朱芳,伍钢,何远桥,等.白花丹醌对肝癌细胞Hep G2增殖及血管内皮生长因子表达的影响[J].中草药,2010,41(5):775-778.
[8]黄慧学.白花丹醌脂质体给药系统的研究[D].南宁:广西医科大学,2008.
[9]Tiwari S B,Pai R M,Udupa N.Temperature sensitive liposomes of plumbagin:Characterization and in vivoevaluation in mice bearing melanoma B16F1[J].J DrugTarget,2002,10(8):585-591.
[10]Aithal B K.Formulation of plumbagin loaded long circulating pegylated liposomes:Evaluation in C57BL/6J mice bearing B16F1 melanoma[J].Drug Deliv,2011,18(7):511-522.
[11]Rayabandla S K M,Aithal K,Anandam A,et al.Preparation,in vitro characterization,pharmacokinetic,and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1melanoma[J].Drug Deliv,2010,17(3):103-113.
[12]Dandawate P,Vemuri K,Venkateswara S K,et al.Synthesis,characterization,molecular docking and antitubercular activity of plumbagin-isoniazid analog and itsβ-cyclodextrin conjugate[J].Bioorg Med Chem Lett,2014,24(21):5070-5075.
[13]魏燕,张永生,郑杭生,等.盐酸青藤碱传递体的制备及其对大鼠类风湿性关节炎的药效评价[J].中草药,2017,48(23):4872-4879.
[14]毛雨婷,纪宏宇,郑东友,等.新型脂质体在经皮给药系统中的应用[J].中国药师,2015,18(12):2141-2144.
[15]王娟,郑杭生,魏燕,等.盐酸青藤碱挥发油边缘活化PEG修饰传递体的离体皮肤渗透研究[J].中草药,2016,47(20):3602-3609.
[16]李莎莎,宋艳丽,危红华,等.传明酸传递体的制备及其性质考察[J].中草药,2013,44(22):3141-3146.
[17]Khan M A,Pandit J,Sultana Y,et al.Novel carbopolbased transfersomal gel of 5-fluorouracil for skin cancer treatment:In vitro characterization and in vivo study[J].Drug Deliv,2015,22(6):795-802.
[18]Shamma R N,Elsayed I.Transfersomal lyophilized gel of buspirone HCl:Formulation,evaluation and statistical optimization[J].J Lipos Res,2013,23(3):244-254.
[19]Wasankar S R.Formulation and development of liposomal gel for topical drug delivery system[J].Int J Pharm Sci Res,2012,3(11):4461-4474.
[20]Widyanati P,Jufri M,Elya B.Formulation and penetration study of liposome gel xanthone of extract mangosteen pericarp(Garcinia mangostana L.)[J].Int J Pharm Sci Rev Res,2014,27(2):1-6.
[21]雷伟,余楚钦,林华庆,等.Box-Behnken响应面法优化他克莫司传递体制备工艺[J].医药导报,2014,33(3):355-360.
[22]曾灿丽.盐酸去氢骆驼蓬碱传递体透皮给药系统及泡囊透皮给药系统的研究[D].乌鲁木齐:新疆医科大学,2013.
[23]陈雯雯,云琦,陶亮,等.小茴香挥发油贴剂体外释放和透皮性能的研究[J].天然产物研究与开发,2016,28(1):65-70.
[24]郭红叶,伊博文,闫小平,等.新型辅料卡波姆在凝胶剂中应用现状[J].中国实验方剂学杂志,2013,19(17):372-374.
[25]熊欣,刘淑芝,顼佳音,等.新型载体经皮凝胶剂的研究进展[J].中国实验方剂学杂志,2011,17(22):244-249.
[26]熊蕊,吴方建.经皮给药系统中新型载体的应用[J].中国药师,2017,20(12):2233-2237.
[2]中华人民共和国卫生部药材标准·维吾尔药分册[S].1999.
[3]云南省中药材标准·第四册[S].2005.
[4]广西中药材标准·第四册[S].1992.
[5]韦燕飞,李景强,张志伟,等.白花丹醌对瘦素刺激的人肝星状细胞周期及其相关蛋白表达的影响[J].中草药,2012,43(9):1776-1780.
[6]史岑慧.白花丹治疗类风湿性关节炎的实验研究[D].广州:广东中医药大学,2013.
[7]朱芳,伍钢,何远桥,等.白花丹醌对肝癌细胞Hep G2增殖及血管内皮生长因子表达的影响[J].中草药,2010,41(5):775-778.
[8]黄慧学.白花丹醌脂质体给药系统的研究[D].南宁:广西医科大学,2008.
[9]Tiwari S B,Pai R M,Udupa N.Temperature sensitive liposomes of plumbagin:Characterization and in vivoevaluation in mice bearing melanoma B16F1[J].J DrugTarget,2002,10(8):585-591.
[10]Aithal B K.Formulation of plumbagin loaded long circulating pegylated liposomes:Evaluation in C57BL/6J mice bearing B16F1 melanoma[J].Drug Deliv,2011,18(7):511-522.
[11]Rayabandla S K M,Aithal K,Anandam A,et al.Preparation,in vitro characterization,pharmacokinetic,and pharmacodynamic evaluation of chitosan-based plumbagin microspheres in mice bearing B16F1melanoma[J].Drug Deliv,2010,17(3):103-113.
[12]Dandawate P,Vemuri K,Venkateswara S K,et al.Synthesis,characterization,molecular docking and antitubercular activity of plumbagin-isoniazid analog and itsβ-cyclodextrin conjugate[J].Bioorg Med Chem Lett,2014,24(21):5070-5075.
[13]魏燕,张永生,郑杭生,等.盐酸青藤碱传递体的制备及其对大鼠类风湿性关节炎的药效评价[J].中草药,2017,48(23):4872-4879.
[14]毛雨婷,纪宏宇,郑东友,等.新型脂质体在经皮给药系统中的应用[J].中国药师,2015,18(12):2141-2144.
[15]王娟,郑杭生,魏燕,等.盐酸青藤碱挥发油边缘活化PEG修饰传递体的离体皮肤渗透研究[J].中草药,2016,47(20):3602-3609.
[16]李莎莎,宋艳丽,危红华,等.传明酸传递体的制备及其性质考察[J].中草药,2013,44(22):3141-3146.
[17]Khan M A,Pandit J,Sultana Y,et al.Novel carbopolbased transfersomal gel of 5-fluorouracil for skin cancer treatment:In vitro characterization and in vivo study[J].Drug Deliv,2015,22(6):795-802.
[18]Shamma R N,Elsayed I.Transfersomal lyophilized gel of buspirone HCl:Formulation,evaluation and statistical optimization[J].J Lipos Res,2013,23(3):244-254.
[19]Wasankar S R.Formulation and development of liposomal gel for topical drug delivery system[J].Int J Pharm Sci Res,2012,3(11):4461-4474.
[20]Widyanati P,Jufri M,Elya B.Formulation and penetration study of liposome gel xanthone of extract mangosteen pericarp(Garcinia mangostana L.)[J].Int J Pharm Sci Rev Res,2014,27(2):1-6.
[21]雷伟,余楚钦,林华庆,等.Box-Behnken响应面法优化他克莫司传递体制备工艺[J].医药导报,2014,33(3):355-360.
[22]曾灿丽.盐酸去氢骆驼蓬碱传递体透皮给药系统及泡囊透皮给药系统的研究[D].乌鲁木齐:新疆医科大学,2013.
[23]陈雯雯,云琦,陶亮,等.小茴香挥发油贴剂体外释放和透皮性能的研究[J].天然产物研究与开发,2016,28(1):65-70.
[24]郭红叶,伊博文,闫小平,等.新型辅料卡波姆在凝胶剂中应用现状[J].中国实验方剂学杂志,2013,19(17):372-374.
[25]熊欣,刘淑芝,顼佳音,等.新型载体经皮凝胶剂的研究进展[J].中国实验方剂学杂志,2011,17(22):244-249.
[26]熊蕊,吴方建.经皮给药系统中新型载体的应用[J].中国药师,2017,20(12):2233-2237.