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Journal of ZheJiang University(Medical Science)  2013, Vol. 42 Issue (5): 523-529    DOI: 10.3785/j.issn.1008-9292.2013.05.008
    
Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug
SUN Xiao-Yi1,  Xiang-Zhi-Qiang1, WU Shuo1, LV Yuan-Yuan1, LIANG Wen-Quan2
1.Department of Pharmacy, School of Medicine, Zhejiang University City College, Hangzhou 310015, China; 2.Institute of Pharmaceutics, College of Pharmacy, Zhejiang University, Hangzhou 310058, China
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Abstract  
Objective: To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug.
Methods: Sub-micro emulsions containing 10% oil, 1.2% lecithin and 2.25% glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated.
Results: Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09±1.98)ng/μg protein which had significant difference with control group \[(38.54±0.34)ng/μg protein\]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73±0.84)ng/μg protein, which was about 3 times of that in anionic emulsions \[(15.71±0.74)ng/μg protein\], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug.
Conclusion: Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination. 


Key wordsCoumarins      Emulsions      Surface-active agents      Hela cells      Biological transport      In vitro     
Received: 03 September 2012      Published: 25 September 2013
CLC:  R 945  
Cite this article:

SUN Xiao-Yi, Xiang-Zhi-Qiang, WU Shuo, LV Yuan-Yuan, LIANG Wen-Quan. Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug. Journal of ZheJiang University(Medical Science), 2013, 42(5): 523-529.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2013.05.008     OR     http://www.zjujournals.com/med/Y2013/V42/I5/523


亚微乳处方因素对亲脂性药物细胞处置的影响

目的:探讨亚微乳处方组成对亲脂性药物细胞摄取和胞内传递过程的影响。
方法:以6-香豆素为模型药物,制备亚微乳。考察油相种类、表面活性剂构成、表面电荷对HeLa细胞摄取的影响,并研究阴离子亚微乳和阳离子亚微乳药物摄取及消除动力学规律,对药物入胞机制进行初步考察。
结果:油相成分和吐温类表面活性剂对细胞摄取无显著影响;司盘类表面活性剂可增加细胞摄取,其中以HLB值为8.6的司盘20效果最好;亚微乳的阳离子修饰可显著增加细胞摄取,加快细胞消除。其摄取速率常数和消除速率常数分别为阴离子亚微乳的4.0倍和1.5倍。6-香豆素主要通过被动扩散方式入胞,阳离子亚微乳细胞摄取增效作用主要通过增加细胞膜接触机会实现。
结论:亚微乳表面特性如乳化剂HLB值及电位可影响亲脂性药物在细胞内的摄取及消除过程。


关键词: 香豆素类,  乳状剂,  表面活性剂,  HeLa细胞,  生物转运,  体外研究 
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