R_8多肽修饰表阿霉素与双氢青蒿素脂质体处方优选及含量测定
|
摘要
目的:优选R_8多肽修饰表阿霉素与双氢青蒿素脂质体的处方,并建立脂质体中表阿霉素的含量测定方法。方法:以薄膜分散法-硫酸铵梯度法制备R_8多肽修饰表阿霉素与双氢青蒿素脂质体,采用星点设计-响应面法对卵磷脂/胆固醇(EPC/Chol)质量比、超声功率、卵磷脂/表阿霉素(EPC/EPI)质量比进行优选,采用高效液相色谱法(HPLC)法测定脂质体中表阿霉素的含量。结果:优选后卵磷脂/胆固醇(EPC/Chol)质量比为4∶1,超声功率为300 W,卵磷脂/表阿霉素(EPC/EPI)质量比为25∶1,所得脂质体平均包封率为(94.5%±0.51%)(n=3);脂质体中表阿霉素的平均含量为(150.01±1.26)μg/mL(n=3)。结论:优化所得处方稳定,适用于制备R_8多肽修饰表阿霉素与双氢青蒿素脂质体;建立的HPLC法准确可靠,简单快速,可用于测定脂质体中表阿霉素的含量。
Objectives:To optimize the formulation of R_8 polypeptide modified epirubicin plus dihydroartemisinin liposomes and to establish a method for determination of epirubin in liposomes. Methods:Thin-film diffusion and ammonium sulfate gradient method were used to prepare R_8 polypeptide modified epirubicin plus dihydroartemisinin liposomes. The central composite design-response surface method was used to optimize the quality ratio of lecithin/cholesterol(EPC/Chol),ultrasonic power and the quality ratio of lecithin/epirubicin(EPC/EPI),and HPLC method was adopted to determine the content of epirubicin.Results:After the optimal formulation,the mass quality ratio of lecithin/cholesterol(EPC/Chol)was 4 ∶1,the ultrasonic power was 300 W,and the mass quality ratio of lecithin/epirubicin(EPC/EPI)was 25∶1. The average encapsulation rate of liposomes was(94.50%±0.51%)(n=3),the average content of epirubicin in liposomes was(150.01±1.26)μg/mL(n=3). Conclution:The optimized formulation stable and suitable for the preparation of R_8 polypeptide modified epirubicin plus dihydroartemisinin liposomes.The established HPLC method is accurate,reliable,simple and rapid,and can be used to determine the content of epirubicin in liposomes.
Objectives:To optimize the formulation of R_8 polypeptide modified epirubicin plus dihydroartemisinin liposomes and to establish a method for determination of epirubin in liposomes. Methods:Thin-film diffusion and ammonium sulfate gradient method were used to prepare R_8 polypeptide modified epirubicin plus dihydroartemisinin liposomes. The central composite design-response surface method was used to optimize the quality ratio of lecithin/cholesterol(EPC/Chol),ultrasonic power and the quality ratio of lecithin/epirubicin(EPC/EPI),and HPLC method was adopted to determine the content of epirubicin.Results:After the optimal formulation,the mass quality ratio of lecithin/cholesterol(EPC/Chol)was 4 ∶1,the ultrasonic power was 300 W,and the mass quality ratio of lecithin/epirubicin(EPC/EPI)was 25∶1. The average encapsulation rate of liposomes was(94.50%±0.51%)(n=3),the average content of epirubicin in liposomes was(150.01±1.26)μg/mL(n=3). Conclution:The optimized formulation stable and suitable for the preparation of R_8 polypeptide modified epirubicin plus dihydroartemisinin liposomes.The established HPLC method is accurate,reliable,simple and rapid,and can be used to determine the content of epirubicin in liposomes.
引文
[1]张阳德,丁诚,张宗久,等.优化工艺制备表阿霉素α-聚氰基丙烯酸正丁酯纳米粒[J].中华实验外科杂志,2006(10):1191-1193.
[2]周敏文,臧宪凌.表阿霉素和阿霉素的特性和毒性比较[J].中国药物与临床,2004(1):61-62.
[3]Evangelatov A,Skrobanska R,Mladenov N,et al. Epirubicin loading in poly(butyl cyanoacrylate)nanoparticles manifests via altered intracellular localization and cellular response in cervical carcinoma(HeLa)cells[J]. Drug Deliv,2016 23(7):2235-2244.
[4]陈召红,刘皈阳,魏亚超.微柱离心高效液相色谱法测定盐酸阿霉素磁性热敏脂质体包封率[J].解放军药学学报,2010,26(6):496-499.
[5]周志敏,崔强,陈欣,等.载表阿霉素聚乳酸微球的制备及性质研究[J].厦门大学学报(自然科学版),2007(2):209-212.
[6]张磊,潘弘,刘敏,等.阿霉素的不同盐型对其脂质体体外药物泄漏和体内长循环的影响[J].药学学报,2004(12):1018-1022.
[7]刘跃亮,罗进勇,张彦,等.双氢青蒿素对人骨肉瘤细胞株143B增殖和凋亡的作用[J].中国药理学通报,2012,28(12):1719-1723.
[8]李惠芝,赵华,邱宗荫,等.高效液相色谱法检测血中表阿霉素的研究[J].重庆医科大学学报,1994(2):79-81.
[9]SHI JF,SUN MG,LI XY,et al. A combination of targeted sunitinib liposomes and targeted vinorelbine liposomes for treating invasive breast cancer[J]. Journal of Biomedi-cal Nanotechnology,2015,11(9):1568-1582.
[10]胡春梅,朱莉,赵俊义,等.粉防己碱脂质体的制备及其稳定性研究[J].中国药房,2008(13):995-997.
[11]李学涛,谭静净,喻荣平,等.中药逆转抗肿瘤药物多药耐药性研究进展[J].辽宁中医药大学学报,2013,15(1):155-158.
[12]贾立峰,李晓明.双氢青蒿素的抗肿瘤作用及机制[J].临床耳鼻咽喉头颈外科杂志,2013,27(18):1033-1036.
[13]邢来全,孙晓圆,张丽.HPLC测定注射用盐酸表柔比星的含量[J].食品与药品,2013,15(3):198-200.
[14]谭静净,程岚,李学涛.中心组合设计-效应面法优化长春碱亲水基修饰阳离子脂质体的处方[J].中草药,2012,43(9):1742-1745.
[15]汤佳明,赵修华,祖元刚.盐酸表阿霉素纳米靶向制剂的缓释效应[J].中国组织工程研究,2013,17(21):3846-3853.
[16]江崇球,高明霞.盐酸表阿霉素与牛血清白蛋白相互作用的研究及药物在血清与尿样中含量的测定[J].光谱学与光谱分析,2003(5):937-940.
[17]齐创,向东华,廖天志.乳腺癌分子分型对多西他赛联合表阿霉素新辅助化疗疗效和预后的预测价值[J].中国肿瘤临床与康复,2016,23(1):17-21.
[18]李春,邱玉琴,杨国忠,等.超高效液相色谱-质谱联用技术同时检测大鼠血浆中蒿甲醚及其主要代谢产物双氢青蒿素[J].分析化学,2015,43(4):588-593.
[19]王保兰,郑玉龙,万玉峰,等.双氢青蒿素干预实验大鼠肺纤维化机制的研究[J].临床肺科杂志,2016,21(10):1828-1832.
[20]贾立峰.双氢青蒿素对头颈部鳞状细胞癌STAT3信号通路的影响及其机制研究[D].重庆:第三军医大学,2016.
[2]周敏文,臧宪凌.表阿霉素和阿霉素的特性和毒性比较[J].中国药物与临床,2004(1):61-62.
[3]Evangelatov A,Skrobanska R,Mladenov N,et al. Epirubicin loading in poly(butyl cyanoacrylate)nanoparticles manifests via altered intracellular localization and cellular response in cervical carcinoma(HeLa)cells[J]. Drug Deliv,2016 23(7):2235-2244.
[4]陈召红,刘皈阳,魏亚超.微柱离心高效液相色谱法测定盐酸阿霉素磁性热敏脂质体包封率[J].解放军药学学报,2010,26(6):496-499.
[5]周志敏,崔强,陈欣,等.载表阿霉素聚乳酸微球的制备及性质研究[J].厦门大学学报(自然科学版),2007(2):209-212.
[6]张磊,潘弘,刘敏,等.阿霉素的不同盐型对其脂质体体外药物泄漏和体内长循环的影响[J].药学学报,2004(12):1018-1022.
[7]刘跃亮,罗进勇,张彦,等.双氢青蒿素对人骨肉瘤细胞株143B增殖和凋亡的作用[J].中国药理学通报,2012,28(12):1719-1723.
[8]李惠芝,赵华,邱宗荫,等.高效液相色谱法检测血中表阿霉素的研究[J].重庆医科大学学报,1994(2):79-81.
[9]SHI JF,SUN MG,LI XY,et al. A combination of targeted sunitinib liposomes and targeted vinorelbine liposomes for treating invasive breast cancer[J]. Journal of Biomedi-cal Nanotechnology,2015,11(9):1568-1582.
[10]胡春梅,朱莉,赵俊义,等.粉防己碱脂质体的制备及其稳定性研究[J].中国药房,2008(13):995-997.
[11]李学涛,谭静净,喻荣平,等.中药逆转抗肿瘤药物多药耐药性研究进展[J].辽宁中医药大学学报,2013,15(1):155-158.
[12]贾立峰,李晓明.双氢青蒿素的抗肿瘤作用及机制[J].临床耳鼻咽喉头颈外科杂志,2013,27(18):1033-1036.
[13]邢来全,孙晓圆,张丽.HPLC测定注射用盐酸表柔比星的含量[J].食品与药品,2013,15(3):198-200.
[14]谭静净,程岚,李学涛.中心组合设计-效应面法优化长春碱亲水基修饰阳离子脂质体的处方[J].中草药,2012,43(9):1742-1745.
[15]汤佳明,赵修华,祖元刚.盐酸表阿霉素纳米靶向制剂的缓释效应[J].中国组织工程研究,2013,17(21):3846-3853.
[16]江崇球,高明霞.盐酸表阿霉素与牛血清白蛋白相互作用的研究及药物在血清与尿样中含量的测定[J].光谱学与光谱分析,2003(5):937-940.
[17]齐创,向东华,廖天志.乳腺癌分子分型对多西他赛联合表阿霉素新辅助化疗疗效和预后的预测价值[J].中国肿瘤临床与康复,2016,23(1):17-21.
[18]李春,邱玉琴,杨国忠,等.超高效液相色谱-质谱联用技术同时检测大鼠血浆中蒿甲醚及其主要代谢产物双氢青蒿素[J].分析化学,2015,43(4):588-593.
[19]王保兰,郑玉龙,万玉峰,等.双氢青蒿素干预实验大鼠肺纤维化机制的研究[J].临床肺科杂志,2016,21(10):1828-1832.
[20]贾立峰.双氢青蒿素对头颈部鳞状细胞癌STAT3信号通路的影响及其机制研究[D].重庆:第三军医大学,2016.