Preparation and Characterization of Glucose Liposome by Supercritical Fluid Technology
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摘要: 脂质体由于其特殊的结构和性能，是一种很有发展潜力的药物载体，在医药和化妆品等行业具有广阔的应用前景。超临界逆向蒸发法是用超临界流体代替有机溶剂制备脂质体的方法，具有对水溶性药物脂质体制备过程简单、包覆率高等特点。以葡萄糖为模型药物，利用该方法制备出了葡萄糖脂质体，并详细考察了不同工艺条件对脂质体粒径和包覆率的影响。结果表明：用超临界逆向蒸发法可成功地制备出最小粒径为290 nm、包覆率最高可达41.3%的葡萄糖脂质体。压力、温度和平衡时间对粒径和包覆率都有较大的影响。压力在10~30 MPa时，随压力的增加，脂质体粒径显著减小至某一值后，基本趋于稳定，而包覆率逐渐增加，达到25.7%~27.5%，随后包覆率逐渐减小；温度在35~65 ℃时，随温度的增加粒径显著减小至最小值，然后逐渐增大，而包覆率一直增大，最高可达41.3%；平衡时间在15~45 min时，随平衡时间的增加，粒径相对稳定，而包覆率显著增加，超过45 min之后，粒径显著增加，包覆率显著下降。Abstract: Liposomes have proven to be promising carriers for their special structure and characterization, and can be widely used in pharmacy and cosmetics.Supercritical reverse phase evaporation (SRPE) is a new technique for preparing liposomes with supercritical fluid instead of organic solvent.The process has characteristic of simple and high coating ratio for water-soluble substances.The technique was used to prepare liposomes with water soluble glucose, and the effects of the process parameters on the particle size and the coating ratio of liposomes were investigated in detail.The liposomes with an average volume diameter of 290-330 nm were successfully prepared by this technique and the coating ratio for water-soluble glucose was as high as 41.3%.It is confirmed that the temperature, pressure and equilibrium time have great effects on the particle size and the coating ratio.As the pressure increased from 10 to 30 MPa, the particle size first decreased remarkably and then kept approximately constant, while the coating ratio gradually increased to 25.7%-27.5% and then gradually decreased; as the temperature increased from 35 to 65 ℃, the particle size decreased obviously to its minimum value and then gradually increased, while the coating ratio increased all along, even to 41.3%.With the equilibrium time increasing from 15 to 45 min, the particle size kept relatively stable, while the coating ratio increased remarkably; when the equilibrium time exceeded 45 min, the particle size increased remarkably, while the coating ratio decreased remarkably.
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Key words:
- supercritical fluid /
- liposome /
- glucose /
- water-soluble drug
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图 1 超临界逆向蒸发过程装置示意图
1.CO2 cylinder；2.High-pressure pump；3.High-pressure gas buffer；4.7.thermostatic water bath；5.High-pressure stop valve；6.Autoclave；8.Pressure gauge；9.Thermometers；10.Backpressure regulator valve；11.Gas flowmeter；12.Gas-liquid separation device
Figure 1. Schematic diagram of experimental setup
图 4 脂质体平均粒径随平衡时间的变化曲线
Figure 4. Effect of equilibrium time on the average size diameter
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[1] Nagayasu A, Uchiyama K. The size of liposomes: A factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs[J]. Adv Drug Delivery Rev, 1999, 40(1/2): 75-87. http://europepmc.org/abstract/med/10837781 [2] 孙聚魁, 邓英杰, 曹金娜.纳米脂质体研究进展[J].沈阳药科大学学报, 2010, 27(12): 993-997, 1002. http://www.cqvip.com/Main/Detail.aspx?id=36272629Sun J K, Deng Y J, Cao J N. Research overviews of nanoliposomes[J]. Journal of Shenyang Pharmaceutical University, 2010, 27(12): 993-997, 1002. (in Chinese) http://www.cqvip.com/Main/Detail.aspx?id=36272629 [3] Zuzanna D K, Agata D J. Liposomes as delivery systems for antibiotics[J]. Int J Pharmac, 2010, 387(1/2): 187-198. [4] 王瑞莲, 刘成梅, 刘伟.脂质体制备方法的研究进展[J].农产品加工·学刊, 2007(8): 12-14.Wang R L, Liu C M, Liu W. Research progress on preparation methods of liposome[J]. Academic Periodical of Farm Products Processing, 2007(8): 12-14. (in Chinese) [5] 邓礼荷, 韦敏燕, 汤晨懿, 等.冻干工艺及保护剂对羟基喜树碱脂质体质量的影响[J].中国医药工业杂志, 2012, 43(1): 30-34. http://www.cnki.com.cn/Article/CJFDTotal-ZHOU201201010.htmDeng L H, Wei M Y, Tang C Y, et al. Effects of lyophilization process and lyoprotectants on the quality of hydroxycamptothecine liposomes[J]. Chinese Journal of Pharmaceuticals, 2012, 43(1): 30-34. (in Chinese) http://www.cnki.com.cn/Article/CJFDTotal-ZHOU201201010.htm [6] 刘晓谦, 王锦玉, 仝燕, 等.脂质体制备技术及其研究进展[J].中国药学杂志, 2011, 46(14): 1084-1088. http://qikan.cqvip.com/Qikan/Article/Detail?id=38631720Liu X Q, Wang J Y, Tong Y, et al. Liposome preparation technology and its research progress[J]. Chinese Pharmaceutical Journal, 2011, 46(14): 1084-1088. (in Chinese) http://qikan.cqvip.com/Qikan/Article/Detail?id=38631720 [7] 张自强, 朱家壁, 姚静, 等. pH梯度法制备伊立替康脂质体[J].中国医科大学学报, 2008, 39(4): 312-316. http://d.wanfangdata.com.cn/Periodical/zgyaokdxxb200804004Zhang Z Q, Zhu J B, Yao J, et al. Preparation of irinotecan liposomes by pH-gradient method[J]. Journal of China Pharmaceutical University, 2008, 39(4): 312-316. (in Chinese) http://d.wanfangdata.com.cn/Periodical/zgyaokdxxb200804004 [8] 李哲, 王绍宁, 黄微葳, 等.盐酸伊立替康脂质体的制备及包封率的测定[J].沈阳药科大学学报, 2011, 28(9): 687-690, 720. http://www.cqvip.com/QK/90654A/20119/39212634.htmlLi Z, Wang S N, Huang W W, et al. Preparation of irinotecan hydrochloride liposomes and quantification of its entrapment efficiency[J]. Journal of Shenyang Pharmaceutical University, 2011, 28(9): 687-690, 720. (in Chinese) http://www.cqvip.com/QK/90654A/20119/39212634.html [9] 程晓丹, 李学明, 顾立.脂质体对水溶性药物包封方法的研究进展[J].华西药学杂志, 2009, 24(2): 194-197. http://www.cnki.com.cn/Article/CJFDTotal-HXYO200902037.htmCheng X D, Li X M, Gu L. Liposome research progress of water-soluble drug coating method[J]. West China Journal of Pharmaceutical Sciences, 2009, 24(2): 194-197. (in Chinese) http://www.cnki.com.cn/Article/CJFDTotal-HXYO200902037.htm [10] Xia F, Jin H Y, Zhao Y P, et al. Supercritical antisolvent-based technology for preparation of vitamin D3 proliposome and its characteristics[J]. Chinese Journal of Chemical Engineering, 2011, 19(6): 1039-1046. doi: 10.1016/S1004-9541(11)60089-X [11] Otake K, Imura T. Development of a new preparation method of Liposomes using supercritical carbon dioxide[J]. Langmuir, 2001, 17: 3898-3901. doi: 10.1021/la010122k [12] Imura T, Otake K. Preparation and physicochemical properties of various soybean lecithin liposomes using supercritical reverse phase evaporation method[J]. Colloids and Surfaces B: Biointerfaces, 2003, 27: 133-140. doi: 10.1016/S0927-7765(02)00048-6 [13] Otake K, Shimomura T. Preparation of liposomes using an improved supercritical reverse phase evaporation method[J]. Langmuir, 2006, 22: 2543-2550. doi: 10.1021/la051654u [14] 陈淑花, 詹世平, 张晶, 等.超临界逆向蒸发法制备葡萄糖脂质体实验及性能表征[J].大连大学学报, 2012, 33(6): 37-40. http://www.cqvip.com/QK/85685X/201206/44045089.htmlChen S H, Zhan S P, Zhang J, et al. Experimental research and properties characterization of the preparation of glucose liposome with the supercritical reverse phase evaporation method[J]. Journal of Dalian University, 2012, 33(6): 37-40. (in Chinese) http://www.cqvip.com/QK/85685X/201206/44045089.html [15] 党奇峰, 刘成圣, 颜景泉, 等.羧甲基壳聚糖包覆VE脂质体的制备及理化性质研究[J].功能材料, 2011, 42(9): 1631-1634. http://www.cqvip.com/qk/89274x/201111/39145563.htmlDang Q F, Liu C S, Yan J Q, et al. The preparation and characterization of CMCS-coated VE liposome[J]. Journal of Functional Materials, 2011, 42(9): 1631-1634. (in Chinese) http://www.cqvip.com/qk/89274x/201111/39145563.html [16] Cevc C, Blume G. Lipid vesicles penetrate into intact skin owning to the transdermal osmotic gtadients and hydration force[J]. Biochim Biophys Acta, 1992, 1104(1): 226-232. doi: 10.1016/0005-2736(92)90154-E -
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