马钱子碱纳米结构脂质载体处方与制备工艺的优化
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摘要
目的优化马钱子碱纳米结构脂质载体(B-NLC)处方与制备工艺。方法溶剂乳化超声法制备B-NLC,以单因素考察法结合星点设计-效应面法(CCD-RSM)优化处方与制备工艺。结果所制备的B-NLC为淡蓝色乳光的透明液体。最优条件为药物用量为1.28 mg,泊洛沙姆188质量浓度为1.08%,固态脂质与液态脂质的比例为1.45∶1,平均粒径为(136.89±4.23)nm,多分散指数(PDI)为0.289±0.005,Zeta电位为(-34.46±0.31)m V,包封率为(68.98±2.06)%,载药量为(1.90±0.06)%。结论溶剂乳化超声法制备的B-NLC包封率高,粒径小,分布均匀,该方法操作简单方便,可以用于B-NLC制备与处方的优化,为马钱子碱的进一步体内研究奠定了基础。
Objective To optimize the prescription and preparation technology of brucine nanostructured lipid carriers(B-NLC). Methods The method of "the solvent emulsification ultrasound" was used to prepare B-NLC. The prescription and preparation was optimized using a single factor method combined with central composite design-response surface methodology(CCD-RSM). Results The resultant B-NLC was transparent liquid with light blue opalescence. The optimal conditions were that the dosage of drugs was 1.28 mg, the mass concentration of poloxamer 188 was 1.08%, and the ratio of solid lipid to liquid lipid was 1.45∶1. The obtained NLC showed the average particle size of(136.89 ± 4.23) nm with a polydispersity index of 0.289 ± 0.005 and a zeta potential of(-34.46 ± 0.31) m V. The entrapment efficiency was calculated to be(68.98 ± 2.06)%, and the drug loading content was(1.90 ± 0.06)%. Conclusion B-NLC prepared by solvent emulsification ultrasound had a high entrapment efficiency and a narrow particle size distribution. The method was easy and simple and can be used to optimize the prescription and preparation of B-NLC, which provides a foundation for the further in vivo research of brucine.
Objective To optimize the prescription and preparation technology of brucine nanostructured lipid carriers(B-NLC). Methods The method of "the solvent emulsification ultrasound" was used to prepare B-NLC. The prescription and preparation was optimized using a single factor method combined with central composite design-response surface methodology(CCD-RSM). Results The resultant B-NLC was transparent liquid with light blue opalescence. The optimal conditions were that the dosage of drugs was 1.28 mg, the mass concentration of poloxamer 188 was 1.08%, and the ratio of solid lipid to liquid lipid was 1.45∶1. The obtained NLC showed the average particle size of(136.89 ± 4.23) nm with a polydispersity index of 0.289 ± 0.005 and a zeta potential of(-34.46 ± 0.31) m V. The entrapment efficiency was calculated to be(68.98 ± 2.06)%, and the drug loading content was(1.90 ± 0.06)%. Conclusion B-NLC prepared by solvent emulsification ultrasound had a high entrapment efficiency and a narrow particle size distribution. The method was easy and simple and can be used to optimize the prescription and preparation of B-NLC, which provides a foundation for the further in vivo research of brucine.
引文
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[18]何晓玮,范晓萍,钟涛,等.马钱子碱新型给药系统治疗类风湿性关节炎的研究进展[J].中华中医药学刊,2015,33(12):2908-2911.
[2]李仙仙,魏武.马钱子碱抗肿瘤及减毒增效的研究进展[J].中国医药指南,2013,11(20):486-487.
[3]李永吉,张欣媛,管庆霞,等.浅议马钱子研究进展[J].中医药学报,2011,39(4):104-106.
[4]曹欢,管庆霞,张亮,等.马钱子新型制剂研究[J].长春中医药大学学报,2014,30(4),622-624.
[5]王海丽,魏武,纪爱芳,等.马钱子碱对人白血病细胞株K562细胞的诱导凋亡作用[J].中国实验血液学杂志,2011,19(3):630-633.
[6]秦建民,杨林,撒忠秋,等.马钱子碱免疫纳米微粒的研制及药代动力学特点[J].中国组织工程研究,2012,16(29):5331-5335.
[7]赵引利,何燕宁,杨宇杰,等.马钱子及其制剂药动学研究进展[J].中草药,2015,36(11):1710-1774.
[8]吴小娟,马凤森,郑高利.马钱子吲哚类生物碱毒性研究进展[J].中药药理与临床,2016,32(6):231-235.
[9]郑娟,沈成英,庞建云,等.丹参酮IIA纳米结构脂质载体的体外评价及其对Ha Ca T细胞增殖的影响[J].中草药,2016,47(24):4340-4344.
[10]高振东.新型纳米结构脂质载体给药系统的研究进展[J].中国药业,2013,22(4):93-94.
[11]刘碧林,石明芯,朱照静,等.星点设计-效应面法优化姜黄素正负离子纳米结构脂质载体处方[J].中草药,2016,47(19):3401-3406.
[12]Vaka S R K,Shivakumar H N,Repka M A,et al.Formulation and evaluation of carnosic acid nanoparticulate system for upregulation of neurotrophins in the brain upon intranasal administration[J].J DrugTarget,2013,21(1):44-53.
[13]Jia L J,Shen J Y,Zhang D R,et al.In vitro and in vivo evaluation of oridonin-loaded long circulating nanostructured lipid carriers[J].Int J Biol Macromol,2012,50(3):523-529.
[14]Eskandari S,Varshosaz J,Minaiyan M,et al.Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers:In vivo pharmacodynamic studies using rat electroshock model[J].Int J Nanomed,2011,6:363-371.
[15]姜雯,曾诚,于宁,等.星点设计-效应面法优化天山雪莲提取物复合磷脂脂质体制备工艺[J].中草药,2016,47(1):57-64.
[16]冯炜玮,陈志伟.固体脂质体纳米粒制备方法的研究进展[J].中国医药生物技术,2011,6(3):218-221.
[17]管庆霞,华晓丹,张喜武,等.HPLC法测定马钱子碱纳米结构脂质载体的主药含量及包封率[J].中国药房,2015,26(21):2983-2986.
[18]何晓玮,范晓萍,钟涛,等.马钱子碱新型给药系统治疗类风湿性关节炎的研究进展[J].中华中医药学刊,2015,33(12):2908-2911.