宝藿苷Ⅰ混合胶束的制备、表征及其体外活性研究

魏渝鉴; 娄彬; 王新东

宝藿苷Ⅰ混合胶束的制备、表征及其体外活性研究

1.
南京医科大学第一临床医学院，江苏南京 210029
2.
南京中医药大学附属第三临床医学院，江苏南京 210028

计量
- 文章访问数: 685
- HTML全文浏览量: 5
- PDF下载量: 615
- 被引次数: 0
出版历程
- 刊出日期: 2016-01-10

Preparation of BaohuosideⅠ-loaded Mixed Micelles and Its Anti-tumor Activity

1.
The First Clinical Medical School, Nanjing Medical University, Nanjing, 210029, China
2.
The Third Clinical Medical School of Nanjing University of Chinese Medicine, Nanjing, 210028, China

摘要

摘要: 目的制备宝藿苷Ⅰ混合胶束，并评价其体外活性。方法采用薄膜水化法制备包载宝藿苷Ⅰ的聚乙二醇-15-羟基硬脂酸酯/泊洛沙姆188混合胶束(BSPM)，通过正交设计法优化BSPM的制备处方和工艺；对该混合胶束的粒径和形态进行表征，并评价其体外释放行为；通过细胞毒性和细胞摄取实验考察宝藿苷Ⅰ混合胶束的体外抗肿瘤活性。结果所制备的BSPM呈球形，形态规则，粒径均一，平均粒径约为33.59 nm，包封率大于80%，BSPM释药缓慢，24 h药物体外释放率为82.56%。BSPM对人乳腺癌MDA-MB-231细胞的细胞毒性和细胞摄取率显著高于宝藿苷Ⅰ原料药。结论 BSPM粒径小，包封率高，可增加宝藿苷Ⅰ的细胞摄取，增强细胞毒性作用，是一种有效的且具有应用前景的抗肿瘤药物制剂。
- 混合胶束 /
- 聚乙二醇-15-羟基硬脂酸酯 /
- 泊洛沙姆188 /
- 抗肿瘤
Abstract: OBJECTIVE Preparation of baohuosideⅠ-loaded mixed micelles and its anti-tumor activity. METHODS BaohuosideⅠ-loaded Solutol HS 15/Poloxamer 188 mixed micelles (BSPM) was prepared by thin-film hydration method and the preparation process of BSPM was optimized by orthogonal design. The formulation of BSPM was evaluated and the in vitro release behavior of BSPM was determined. Cell toxicity and uptake assays were employed to evaluate the anti-tumor activities. The targeting effect of BSPM was studied by fluorescence labeling. RESULTS The BSPM prepared showed spherical and regular shape， with an average particle size of 33.59 nm and its entrapment efficiency more than 80%. The 24 h-accumulated release ratio in vitro of BSPM was up to 82.56%. Cytotoxicity of BSPM on human breast cancer cell line MDA-MB-231 was significantly stronger than that of free baohuosideⅠ and the uptake rate was improved. CONCLUSION The BSPM which shows small particle size and high entrapment efficiency can enhance cell toxicity and uptake. It is an effective and promising formulation for anti-tumor drug.
- mixed micelles /
- Solutol HS15 /
- Poloxamer 188 /
- anti-tumor

HTML全文

参考文献(21)

[1]	Qian Q， Li SL， Sun E， et al. Metabolite profiles of icariin in rat plasma by ultra-fast liquid chromatography coupled to triple-quadrupole/time-of-flight mass spectrometry[J]. J Pharm Biomed Anal， 2012， 66:392-398.
[2]	Zhai YK， Guo X， Pan YL， et al. A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy[J]. Pharmazie， 2013， 68(9): 713-722.
[3]	Yu XB， Tong Y， Han XQ， et al. Anti-angiogenic activity of Herba Epimedii on zebrafish embryos in vivo and HUVECs in vitro[J]. Phytother Res， 2013， 27(9): 1368-1375.
[4]	Xiao HH， Fung CY， Mok SK， et al. Flavonoids from Herba epimedii selectively activate estrogen receptor alpha (ER alpha) and stimulate ER-dependent osteoblastic functions in UMR-106 cells[J]. J Steroid Biochem， 2014， 143: 141-151.
[5]	Song J， Shu L， Zhang ZH， et al. Reactive Oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer[J]. Chem Biol Interact， 2012， 199(1): 9-17.
[6]	Kim SH， Ahn KS， Jeong SJ， et al. Janus activated kinase 2/signal transducer and activator of transcription 3 pathway mediates icariside II-induced apoptosis in U266 multiple myeloma cells[J]. Eur J Pharmacol， 2011， 654(1): 10-16.
[7]	Choi HJ， Eun JS， Kim DK， et al. Icariside II from Epimedium koreanum inhibits hypoxia-inducible factor-1 alpha in human osteosarcoma cells[J]. Eur J Pharmacol， 2008， 579(1/3): 58-65.
[8]	Jin X， Zhang ZH， Sun E， et al. Preparation of a nanoscale baohuosideⅠ- phospholopid complex and determination of its absoption: in vivo and in vitro evaluations[J]. Int J Nanomed， 2012， 7: 4907-4916.
[9]	Liu YQ， Yang QX， Cheng MC， et al. Synergistic inhibitory effect of Icariside II with Icaritin from Herba Epimedii on pre-osteoclastic RAW264.7 cell growth[J]. Phytomedicine， 2014， 21(12): 1633-1637.
[10]	严红梅，孙娥，宋捷，等．宝藿苷Ⅰ磷脂复合物的制备及其抗肿瘤活性的初步研究[J]．中国药学杂志，2014， 49（19）：1725-1728．
[11]	Yan HM， Sun E， Song J， et al. Physicochemical properties of baohuoside Ⅰ phytosomes and its anti-tumor activity[J]. Chin Pharm J， 2014， 49(19): 1725-1728.
[12]	Wu WT， Shi WJ， Wu QZ. Preparation and in vitro evaluation of docetaxel-loaded solutol HS15/pluronic F127 mixed micelles[J]. Prog Phar Sci， 2013， 37(5): 222-228.
[13]	崔亚男，葛建君，李凌冰．紫杉醇混合胶束的制备及增强口服生物利用度研究[J]．山东大学学报:医学版，2012， 50（11）：107-112．
[14]	Cui YN， Ge JJ， Li LB. Preparation of paclitaxel-loaded mixed micelles and enhancement on oral absorption of paclitaxel[J]. J Shandong Univ: Med Sci， 2012， 50(11): 107-112.
[15]	刘洁凝，刘珊珊，吴琼珠，等．多西紫杉醇前体混合胶束的制备及体外评价[J]．中国药科大学学报，2010， 41（3）：240-243．
[16]	Liu JN， Liu SS， Wu QZ， et al. Preparation and in vitro evaluation of pro-mixed docetaxel micelles[J]. J China Pharm Univ， 2010， 41(3): 240-243.
[17]	Illum L， Jordan F， Lewis AL. CriticalSorb:a novel efficient nasal delivery system for human growth hormone based on Solutol HS15[J]. J Controll Release， 2012， 162(1): 194-200.
[18]	魏平平，张振海，金鑫，等．木犀草素混合胶束的制备及其抗肿瘤活性研究[J]．中国药学杂志，2015， 50（15）：1330-1334．
[19]	Wei PP， Zhang ZH， Jin X， et al. Preparation of luteolin-loaded mixed miceHes and their anti-tumor activity[J]. Chin Pharm J， 2015， 50(15): 1330-1334.
[20]	王猛，张钧寿，周建平．注射用辅料泊洛沙姆188[J]．药学与临床研究，2007， 15（1）：10-13．
[21]	Wang M， Zhang JS， Zhou JP. An injectable excipient： poloxamer 188[J]. Pharm Clin Res， 2007， 15(1): 10-13.