维生素C脂质体的研究
摘要
本课题主要对维生素C脂质体进行了研究,在考察维生素C稳定性、筛选脂质体膜材料、确定制备方法和包封率测定方法的基础上,采用单因素实验和响应面分析实验相结合,确定维生素C脂质体的最佳制备条件,再用聚乙二醇对维生素C脂质体进行表面包覆,显著提高了维生素C脂质体的稳定性。
维生素C在避光、低温、酸性和中性条件下比较稳定,24h后保存率仍能在90%以上。烷基糖苷、span系列表面活性剂、tween系列表面活性剂、卵磷脂四种膜材料制备的脂质体中,卵磷脂制备的稳定性最好。维生素C比较容易氧化,所以采用薄膜分散-超声乳化法制备脂质体。用截留分子量为3500的透析袋在去离子水中透析16h,然后用反相高效液相色谱法测定未包封的维生素C含量,计算包封率。
单因素实验和响应面分析实验相结合,确定维生素C脂质体的最佳制备条件为:卵磷脂和胆固醇的质量比为9.61︰1、PBS的pH值为6.52、维生素C的质量为1.28g。在此条件下,制得的维生素C脂质体平均包封率为41.47%,与最大预测值41.61%比较接近,并且重现性良好。
按最佳制备条件制得维生素C脂质体后,将PEG溶液与维生素C脂质体混合制备PEG包覆的脂质体。并得到最适于包覆维生素C脂质体的是PEG1500,且当PEG1500的质量分数为3 %时,包封率最高为56.88 %。
对维生素C脂质体以及聚乙二醇包覆的维生素C脂质体进行显微形态观察,得到脂质体均为圆球状,PEG1500包覆的脂质体在脂质体外层形成了一个PEG包覆层。激光粒度仪测定结果显示,维生素C脂质体平均粒径约300nm;PEG1500包覆的维生素C脂质体平均粒径约450nm,脂质体经PEG包覆后粒径增大。
通过对粒径、泄漏率、MDA值的测定研究了脂质体的物理、化学短期稳定性。随着时间的增长,脂质体粒子会聚集、融合,粒径增大;泄漏率增加;膜材磷脂有一定程度氧化,MDA值增加;但经PEG1500包覆后,明显抑制了脂质体的聚集、融合,减缓了维生素C的泄漏和MDA值的增加。
In this paper, vatimin C-containing lipome was researched. On the basis of studying the stability of vitamin C, choosing the proper film material of lipome and the methods for preparing liposome and measuring encapsulation, one-factor tests and response surface analysis were carried out to get optimum conditions.Then the stability of vitamin C-containing liposome was evidently improved by coating PEG.
Under the light-avoiding, low-temperature, acidic or neutral condition, vitamin C was stable and its preservation rate was still above 90% in 24 hours. Comparing with the liposomes which were prepared by alkylpolyglucosides, span and tween surfactants, the liposome prepared with lecithin had better stability. The film dispersion-ultrasonic emulsify method was taken, because of the stability of vitamin C. The free vitamin C was separated from liposome by dialysis in deionized water for 16 hours, and the encapsulation was measured by RP-HPLC.
The optimum conditions determined by one-factor tests and response surface analysis were as follow: the ratio of lecithin and cholesterol was 9.61︰1(w/w), pH of PBS was 6.52 and the quality of vitamin C was 1.28g. The encapsulatin of vitamin C liposome prepared under this condition was 41.47% averagely, close to 41.61% resulted from response surface analysis. And the result recured all right. The PEG-coated vitamin C-containing liposome was prepared by simply mixing the liposomal suspension with the PEG solution. The best PEG for coating was PEG1500, and when its concemtration was 3%, the encapsulation was 56.88% maximally.
The structure determined by electron microscope confirmed the existence of polymer on the surface of liposome particles and those particals were in the shape of pellet. By comparison with the non-coated liposome whose diameter was 300nm approximately, the polymer coated one with 450nm had larger particle size.
The physical and chemical stability of lipome was investigated by measuring the changes of diameter, leakage rate and the malondialdehyde(MDA) content. With the time going up, the particals would assemble, the leakage rate would increase and the lecithin would be oxidated. However, these changes were evidently restrained by coating PEG 1500.
维生素C在避光、低温、酸性和中性条件下比较稳定,24h后保存率仍能在90%以上。烷基糖苷、span系列表面活性剂、tween系列表面活性剂、卵磷脂四种膜材料制备的脂质体中,卵磷脂制备的稳定性最好。维生素C比较容易氧化,所以采用薄膜分散-超声乳化法制备脂质体。用截留分子量为3500的透析袋在去离子水中透析16h,然后用反相高效液相色谱法测定未包封的维生素C含量,计算包封率。
单因素实验和响应面分析实验相结合,确定维生素C脂质体的最佳制备条件为:卵磷脂和胆固醇的质量比为9.61︰1、PBS的pH值为6.52、维生素C的质量为1.28g。在此条件下,制得的维生素C脂质体平均包封率为41.47%,与最大预测值41.61%比较接近,并且重现性良好。
按最佳制备条件制得维生素C脂质体后,将PEG溶液与维生素C脂质体混合制备PEG包覆的脂质体。并得到最适于包覆维生素C脂质体的是PEG1500,且当PEG1500的质量分数为3 %时,包封率最高为56.88 %。
对维生素C脂质体以及聚乙二醇包覆的维生素C脂质体进行显微形态观察,得到脂质体均为圆球状,PEG1500包覆的脂质体在脂质体外层形成了一个PEG包覆层。激光粒度仪测定结果显示,维生素C脂质体平均粒径约300nm;PEG1500包覆的维生素C脂质体平均粒径约450nm,脂质体经PEG包覆后粒径增大。
通过对粒径、泄漏率、MDA值的测定研究了脂质体的物理、化学短期稳定性。随着时间的增长,脂质体粒子会聚集、融合,粒径增大;泄漏率增加;膜材磷脂有一定程度氧化,MDA值增加;但经PEG1500包覆后,明显抑制了脂质体的聚集、融合,减缓了维生素C的泄漏和MDA值的增加。
In this paper, vatimin C-containing lipome was researched. On the basis of studying the stability of vitamin C, choosing the proper film material of lipome and the methods for preparing liposome and measuring encapsulation, one-factor tests and response surface analysis were carried out to get optimum conditions.Then the stability of vitamin C-containing liposome was evidently improved by coating PEG.
Under the light-avoiding, low-temperature, acidic or neutral condition, vitamin C was stable and its preservation rate was still above 90% in 24 hours. Comparing with the liposomes which were prepared by alkylpolyglucosides, span and tween surfactants, the liposome prepared with lecithin had better stability. The film dispersion-ultrasonic emulsify method was taken, because of the stability of vitamin C. The free vitamin C was separated from liposome by dialysis in deionized water for 16 hours, and the encapsulation was measured by RP-HPLC.
The optimum conditions determined by one-factor tests and response surface analysis were as follow: the ratio of lecithin and cholesterol was 9.61︰1(w/w), pH of PBS was 6.52 and the quality of vitamin C was 1.28g. The encapsulatin of vitamin C liposome prepared under this condition was 41.47% averagely, close to 41.61% resulted from response surface analysis. And the result recured all right. The PEG-coated vitamin C-containing liposome was prepared by simply mixing the liposomal suspension with the PEG solution. The best PEG for coating was PEG1500, and when its concemtration was 3%, the encapsulation was 56.88% maximally.
The structure determined by electron microscope confirmed the existence of polymer on the surface of liposome particles and those particals were in the shape of pellet. By comparison with the non-coated liposome whose diameter was 300nm approximately, the polymer coated one with 450nm had larger particle size.
The physical and chemical stability of lipome was investigated by measuring the changes of diameter, leakage rate and the malondialdehyde(MDA) content. With the time going up, the particals would assemble, the leakage rate would increase and the lecithin would be oxidated. However, these changes were evidently restrained by coating PEG 1500.
引文
[1]高春芳,汪昌国,朱海洋.亮丽的活性物载体-多彩软球[J].日用化学品科学,2004,11:36-38.
[2]吕洛,魏少敏,林惠芬等.脂质体载药系统经皮给药的研究进展[J].日用化学工业,2002,32(5):51-54.
[3]张灵芝.脂质体制备及其在生物医学中的应用[M].北京:北京医科大学、中国协和医科大学联合出版社,1998.1,57-58.
[4] Gabriele Betz,Angela Aeppli,Natalia Menshutina,etc.In vivo comparison of various liposome formulations for cosmetic application[J].International Journal of Pharmaceutics, 2005(296): 44–54.
[5]余爱农,张庆.精细化工制剂成型技术[M].北京:化学工业出版社,2002.499-503..
[6] Aranya Manosroi,Paveena Wongtrakul,Jiradej Manosroi,etc.Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol[J].Colloids and Surfaces B,2003,30:129-138.
[7]姜树红,戈延茹,汪珠燕.非离子表面活性剂囊泡的研究进展[J].中国现代药物应用,2007,1(11):98-101.
[8]穆筱梅.脂质体在化妆品中的应用[J].广东化工,2006,33(2):20-22.
[9]郑宁,张立德.脂质体质量控制方法的研究概况[J].中国新药杂志,2004,13(12):1282-1286.
[10] Agustina Gomez-Hens,Juan Manuel Fernandez-Romero.The role of liposomes in analytical process[J].Trends in Analytical Chemistry,2005,24(1):9-19.
[11]朱全刚,胡晋红.来氟米特脂质体的工艺优化[J].华西药学杂志,2000,15(2):85-88.
[12] Bajoria R,Soli F.Effect of t he size of liposomes on the transfer and uptake of carboxyfluorescein by the perfused human term placenta[J].The Journal of pharmacy and pharmacology,1997,49(7):675-681.
[13] Sergey P.Radko,Andreas Chrambach. Capillary electrophoresis (CE) of subcellular-sized particles[J].Journal of Chromatography B:Biomedical Sciences and Applications,1999,722(1-2):1-10.
[14] A.Memoli,L.G.Palermiti,V.Travagli,etc.Egg soya phospholipids-sonication and dialysis:A study on liposome characterization[J].international journal of pharmaceutics,1995,117:159-163.
[15]高晓黎,季兴梅.葡聚糖凝胶柱色谱法测定脂质体包封率的条件筛选[J].中国药学杂志,2003,38(7):515-517.
[16]赵荣生,严宝霞,候新朴.两性霉素B脂质体的研制及其质量评价[J].中国药学杂志,2000,35(9):593-595.
[17]李凤,林建英,李彦威.更昔洛韦脂质体的制备[J].西北药学杂志,2007,22(6):317-319.
[18]夏书芹,许时婴.辅酶Q10纳米脂质体稳定性的研究[J].食品与机械,2006,32(3):28-32.
[19]曹宁宁,羡菲,刘金鹏.脂质体的制备方法及研究进展[J].天津理工学院学报,2003,19(1):30-35.
[20] V.P.托尔钦林,V.魏西希主编.脂质体[M].原著第二版.邓意辉,徐晖主译.北京:化学工业出版社,生物·医药出版分社,2007.7-8.
[21]赵海霞,郭兴奎,孔德亮.脂质体制备技术[J].山东中医杂志,2000,19(7):435-437.
[22]刘朝晖,王栋.脂质体技术及其在生物医学中的应用[J].承德医学院学报,2004,21(2):168-169.
[23]蔡钦生,黄海,冯美卿等.那西肽脂质体的制备及其体外抗乙肝病毒的研究[J].药学学报,2005,40(5):462-465.
[24]刘树葆.包囊技术及在化妆品中的应用[J].日用化学工业,1999,4(2):60-62.
[25] Eric M,Vuckovic N,Pilija V,etc.Occurrence of congenital malformations in dead fetuses and neonates autopsied between 1991 and 2001 at the Institute of Pathology and Histology in Novi Sad[J].Med Pregl,2003,56(7-8):373-376.
[26]施靖,王红芳.脂质体作为药物载体的研究[J].中国医药导报,2008,5(11):29-30.
[27]张天民,邹立家,翟光喜.低分子肝素脂质体的研究[J].中国药学杂志,2001,36( 5) :316- 318.
[28]王弘,王志清. pH-敏脂质体研究的最新进展[J].中国新药杂志,1999,8(7):439- 441.
[29]车晓平,赵小伟,李卫敏.脂质体在皮肤局部给药系统中的应用[J].北京中医药,2008,27(4):289-291.
[30]黄黎,李成文.脂质体在医学中的应用进展[J].国际生物制品学杂志,2006, 29(3):130.
[31] Hsiu Ying Yu, Hui Min Liao. Triamcinolone permeation from different liposome formulations through rat skin in vitro[J].International Journal of Pharmaceutics, 1996, 127(1):1-7.
[32]郭清,林惠芬,高申等.化妆品功能性成分经皮给药与研究[J].香料香精化妆品,2002,2(1):32-34.
[33]姚殿军,俞路.脂质体及其在化妆品中的应用[J].日用化学工业,1994,6:32-36.
[34]张根旺,刘晓见.脂质体化妆品及其应用[J] .郑州工程学院院报,2000,21(4):1-4
[35] Branka Katusin-Razem, Branka Mihaljevic, Dusan Razem.Microbial decontamination of cosmetic raw materials and personal care products by irradiation[J]. Radiation Physics and Chemistry , 2003, 66(4): 309–316.
[36] Ruzica Galovic Rengel,Jelena Filipovic-Grcic,Ivana Cepelak,etc.The effect of liposomes with superoxide dismutase on A2182 cells[J].European Journal of Pharmaceutics and Biopharmaceutics,2005,60:47-51.
[37]严勇朝,解素花,白杰英等.脂质体—一种新型的化妆品体系[J].北京日化,2002,2:19-23.
[38]于波涛,张志荣,曾仁杰等.脂质体稳定性的研究进展[J].西南国防医药,2005,15(6):686-688.
[39] Seiichiro Minato,Kazunori Iwanaga,Masawo Kakemi,etc.Application of polyethyleneglycol(PEG)-modified liposomes for oral vaccine:effect of lipid dose on systemic and mucosal immunity[J].Journal of controlled release,2003,89:189-197.
[40] Jun-Mei Zhang.Effect of Amphipathic PEG-PE on the Circulation Time of Liposomes in vivo[J].Journal of Chinese Pharmaceutical Sciences,1996,5(2):111.
[41]李先红,李国栋.聚乙二醇包覆的醋酸泼尼松龙纳米脂质体的制备及性能研究[J].襄樊学院学报,2006,27(2).
[42]李慧良,高申,陈建民等.维生素A神经酰胺脂质体的初步研究[J].日用化学品科学,2007,30(9):15-17.
[43] Sophia Hatziantoniou,loannis P.Nezis,Lukas H.Margaritis,etc.Visualisation of liposomes prepared from skin and stratum corneum lipids by transmission electron microscopy[J].micron,2007,38(8):777-781.
[44]穆筱梅.聚乙烯醇修饰维生素E脂质体的制备及性质研究[J].香料香精化妆品,2007,12(6):23-25.
[45]曾翔云.维生素C的生理功能与膳食保障[J].中国食物与营养,2005,4:52-54.
[46]任欢鱼,韦异,朱海洋.维生素在皮肤护理中的应用[J].公司专栏,2004,11(15):40-42.
[47]裘炳毅.化妆品化学与工艺技术大全[M].北京:中国轻工业出版社,1997.629-630.
[48]章苏宁.化妆品工艺学[M].北京:中国轻工业出版社,2007.197-198.
[49] Elizabeth A.Offord,Jean-Charles Gautier,Ornella Avanti,etc.Photoprotective potential of lycopene,β-carotene,vitamin E,vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts[J].Free Radical Biology and Medicine, 2002, 32(12): 1293-1303.
[50] Ntei Abudu,James J.Miller,Mohammed Attaelmannan,etc.Vitamins in human arteriosclerosis with emphasis on vitamin C and vitamin E[J]. Clinica Chimica Acta, 2004,339(1-2):11-25.
[51] Ahmed S.Guinedi, Nahed D.Mortada, Samar Mansour,etc.Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide[J]. International Journal of Pharmaceutics,2005,306(1-2):71-82.
[52]杜美菊,王亚婷,赵凤林等.非离子表面活性剂囊泡对头孢菌素药物的缓释作用[J].化学研究,2005,16(3):67-70.
[53]赵晓宇,李慧,张保献.新型药物载体非离子囊泡的制备和评价研究进展[J].国际药学研究杂志,2007,34(6):439-443.
[54] Rita Cortesi,Elisabetta Esposito,Francesca Corradini,etc.Non-phospholipid vesicles as carriers for peptides and proteins:Production,characterization and stability studies[J]. International Journal of Pharmaceutics,2007,339(1-2):52-60
[55] Yongmei Hao,Fenglin Zhao,Na Li,etc.Studies on a high encapsulation of colchicines by a noisome system[J]. International Journal of Pharmaceutics,2002,244(1-2):73-80.
[56] Maria Manconi, Chiara Sinico, Donatella Valenti,etc. Niosomes as carriers for tretinoin: III. A study into the in vitro cutaneous delivery of vesicle-incorporated Maria Manconi, Chiara Sinico [J].International Journal of Pharmaceutics,2006,311(1-2): 11-19.
[57] Julijana Kristl,Breda Volk,Mirjana Gasperlin,etc.Effect of colloidal carriers on ascorbyl palmitate stability[J]. European Journal of Pharmaceutical Sciences,2003,19(4):181-189.
[58]龚盛昭.天然活性化妆品的概况和发展前景[J].香精香料化妆品,2002,4(2):16-19.
[59] A.Manosroi,K.Podjanasoonthon,J.Manosroi.Development of novel topical tranexamic acid liposome formulations[J]. International Journal of Pharmaceutics,2002,235:61-70.
[60]张蓓,王东凯,刘淑平等.硫酸多粘菌素E脂质体的制备及含量和包封率的测定[J].药物分析杂志,2005,25(8):920-923.
[61]王玉梅,郭桥,李秀芝等.干扰素脂质体的制备及理化性质分析[J].中国生物制品学杂志,2005.18(2):141-142.
[62]段逸松,张志荣.米托蒽醌脂质体制备工艺的研究[J].华西药学杂志,2001,16(2):91-92.
[63] Alma Foco,Mirjana Gasperlin,Julijana Kristl.Investigation of liposomes as carriers of sodium ascorbyl phosphate for cutaneous photoprotection[J]. International Journal of Pharmaceutics,2005,291:21-29.
[64]姜素芳,姚瑶,丁燕飞等.反相高效液相色谱法测定盐酸青藤碱纳米脂质体药物含量及包封率[J].中南药学,2005,3(4):213-216.
[65]穆筱梅,钟振声,陈焕钦.果酸脂质体的制备、检测及应用[J].香精香料化妆品,2002,5:25-27.
[66]王岩,周莉玲.青藤碱脂质体的制备及稳定性研究[J].中成药,2005,25(7):757-760.
[67]汪怡芳.半胱胺脂质体的研制[D]:[硕士学位论文].江苏:江南大学,2001.
[68]周国仪,舒静,黄泽元.响应面法优化超声提取芝麻叶黄酮的研究[J].食品与机械,2007, 23(3):77-80.
[69]袁超,金征宇.响应面法优化羟丙基-β-环糊精制备工艺[J].食品科学,2007,28(3):147-151.
[70] Mahesh N.Padamwar,Varsha B.Pokharkar.Development of vitamin loaded topical liposomal formulation using factorial design approach:Drug deposition and stability[J]. International Journal of Pharmaceutics,2006,320:37-44.
[71]吴有炜.试验设计与数据处理[M].苏州:苏州大学出版社,2002.135-143.
[72]余旭亚,赵声兰,李涛等.仙人掌SOD脂质体的制备研究[J].昆明理工大学学报,2002,27(1):103-105.
[73]郭海燕,莫穗林.脂质体物理稳定性和包封率的影响因素[J].中国新药杂志,2004,13(6):498-501.
[74]穆筱梅.聚乙烯醇修饰脂质体的制备研究[D]:[博士学位论文].广州:华南理工大学,2004.
[75]阮征,胡筱波,赖富饶等.油菜花粉中黄酮类物质提取工艺的优化研究[J].食品科学,2007,28(7):133-137.
[76]高静,姜艳军,周丽亚等.维生素C乳酸酯酶催化合成的相应曲面分析[J].精细化工,2006,23(9):916-920.
[77]陈钢,陈红兰,苏伟等.响应面分析法优化黄精多糖提取工艺参数[J].食品科学,2007,28(7):198-201.
[78] Martin C Woodle,Danile D Lasic.Sterically stabilized liposome[J].Biochimica et Biophysica Acta,1992,1113:171-199.
[79] Maria H.A.Zanin,Iris C.L.Torriani,Ricardo L.Zollner,et al.Physical characterization of surface-modified liposomes by incorporation of gangliosides designed for immunotherapies[J]. Colloids and Surfaces A: Physicochem.Eng.Aspects, 2004,251:175-182.
[80] Olga Garbuzenko,Yechezkel Barenholz,Aba Priev.Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer[J]. Chemistry and Physics of Lipids,2005,135:117-129.
[81]史向阳,孙曹民,吴世康.胶原、壳聚糖包覆的小单层脂质体的体外稳定性评价[J].生物物理学报,1998,14(4):635-641.
[82] Hirofumi Takeuchi,Hiromitsu Yamamoto,Toshitada Toyoda,etc.Physical stability of size controlled small unilameller liposomes coated with a modified polyvinyl alcohol[J]. International Journal of Pharmaceutics,1998,164:103-111.
[83]朱斌,许时婴,夏书芹.薄膜水化法制备辅酶Q10脂质体[J].食品与机械,2006,22(6):39-41.
[84] S.L.Law,K.J.Huang,H.Y.Chou.Preparation of desmopressin-containing liposomes for intranasal delivery[J].Journal of control release,2001,70:375-382.
[85]孙京新,周光宏,徐幸莲.猪肉微粒体脂肪酸氧化产物对氧合肌红蛋白氧化的影响[J].南京农业大学学报,2004,27(1):101-104.
[86]陈涛,王昭,傅经国等.聚乙二醇修饰脂质体研究[J].世界最新医学信息文摘,2003,2(5):801-805.
[2]吕洛,魏少敏,林惠芬等.脂质体载药系统经皮给药的研究进展[J].日用化学工业,2002,32(5):51-54.
[3]张灵芝.脂质体制备及其在生物医学中的应用[M].北京:北京医科大学、中国协和医科大学联合出版社,1998.1,57-58.
[4] Gabriele Betz,Angela Aeppli,Natalia Menshutina,etc.In vivo comparison of various liposome formulations for cosmetic application[J].International Journal of Pharmaceutics, 2005(296): 44–54.
[5]余爱农,张庆.精细化工制剂成型技术[M].北京:化学工业出版社,2002.499-503..
[6] Aranya Manosroi,Paveena Wongtrakul,Jiradej Manosroi,etc.Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol[J].Colloids and Surfaces B,2003,30:129-138.
[7]姜树红,戈延茹,汪珠燕.非离子表面活性剂囊泡的研究进展[J].中国现代药物应用,2007,1(11):98-101.
[8]穆筱梅.脂质体在化妆品中的应用[J].广东化工,2006,33(2):20-22.
[9]郑宁,张立德.脂质体质量控制方法的研究概况[J].中国新药杂志,2004,13(12):1282-1286.
[10] Agustina Gomez-Hens,Juan Manuel Fernandez-Romero.The role of liposomes in analytical process[J].Trends in Analytical Chemistry,2005,24(1):9-19.
[11]朱全刚,胡晋红.来氟米特脂质体的工艺优化[J].华西药学杂志,2000,15(2):85-88.
[12] Bajoria R,Soli F.Effect of t he size of liposomes on the transfer and uptake of carboxyfluorescein by the perfused human term placenta[J].The Journal of pharmacy and pharmacology,1997,49(7):675-681.
[13] Sergey P.Radko,Andreas Chrambach. Capillary electrophoresis (CE) of subcellular-sized particles[J].Journal of Chromatography B:Biomedical Sciences and Applications,1999,722(1-2):1-10.
[14] A.Memoli,L.G.Palermiti,V.Travagli,etc.Egg soya phospholipids-sonication and dialysis:A study on liposome characterization[J].international journal of pharmaceutics,1995,117:159-163.
[15]高晓黎,季兴梅.葡聚糖凝胶柱色谱法测定脂质体包封率的条件筛选[J].中国药学杂志,2003,38(7):515-517.
[16]赵荣生,严宝霞,候新朴.两性霉素B脂质体的研制及其质量评价[J].中国药学杂志,2000,35(9):593-595.
[17]李凤,林建英,李彦威.更昔洛韦脂质体的制备[J].西北药学杂志,2007,22(6):317-319.
[18]夏书芹,许时婴.辅酶Q10纳米脂质体稳定性的研究[J].食品与机械,2006,32(3):28-32.
[19]曹宁宁,羡菲,刘金鹏.脂质体的制备方法及研究进展[J].天津理工学院学报,2003,19(1):30-35.
[20] V.P.托尔钦林,V.魏西希主编.脂质体[M].原著第二版.邓意辉,徐晖主译.北京:化学工业出版社,生物·医药出版分社,2007.7-8.
[21]赵海霞,郭兴奎,孔德亮.脂质体制备技术[J].山东中医杂志,2000,19(7):435-437.
[22]刘朝晖,王栋.脂质体技术及其在生物医学中的应用[J].承德医学院学报,2004,21(2):168-169.
[23]蔡钦生,黄海,冯美卿等.那西肽脂质体的制备及其体外抗乙肝病毒的研究[J].药学学报,2005,40(5):462-465.
[24]刘树葆.包囊技术及在化妆品中的应用[J].日用化学工业,1999,4(2):60-62.
[25] Eric M,Vuckovic N,Pilija V,etc.Occurrence of congenital malformations in dead fetuses and neonates autopsied between 1991 and 2001 at the Institute of Pathology and Histology in Novi Sad[J].Med Pregl,2003,56(7-8):373-376.
[26]施靖,王红芳.脂质体作为药物载体的研究[J].中国医药导报,2008,5(11):29-30.
[27]张天民,邹立家,翟光喜.低分子肝素脂质体的研究[J].中国药学杂志,2001,36( 5) :316- 318.
[28]王弘,王志清. pH-敏脂质体研究的最新进展[J].中国新药杂志,1999,8(7):439- 441.
[29]车晓平,赵小伟,李卫敏.脂质体在皮肤局部给药系统中的应用[J].北京中医药,2008,27(4):289-291.
[30]黄黎,李成文.脂质体在医学中的应用进展[J].国际生物制品学杂志,2006, 29(3):130.
[31] Hsiu Ying Yu, Hui Min Liao. Triamcinolone permeation from different liposome formulations through rat skin in vitro[J].International Journal of Pharmaceutics, 1996, 127(1):1-7.
[32]郭清,林惠芬,高申等.化妆品功能性成分经皮给药与研究[J].香料香精化妆品,2002,2(1):32-34.
[33]姚殿军,俞路.脂质体及其在化妆品中的应用[J].日用化学工业,1994,6:32-36.
[34]张根旺,刘晓见.脂质体化妆品及其应用[J] .郑州工程学院院报,2000,21(4):1-4
[35] Branka Katusin-Razem, Branka Mihaljevic, Dusan Razem.Microbial decontamination of cosmetic raw materials and personal care products by irradiation[J]. Radiation Physics and Chemistry , 2003, 66(4): 309–316.
[36] Ruzica Galovic Rengel,Jelena Filipovic-Grcic,Ivana Cepelak,etc.The effect of liposomes with superoxide dismutase on A2182 cells[J].European Journal of Pharmaceutics and Biopharmaceutics,2005,60:47-51.
[37]严勇朝,解素花,白杰英等.脂质体—一种新型的化妆品体系[J].北京日化,2002,2:19-23.
[38]于波涛,张志荣,曾仁杰等.脂质体稳定性的研究进展[J].西南国防医药,2005,15(6):686-688.
[39] Seiichiro Minato,Kazunori Iwanaga,Masawo Kakemi,etc.Application of polyethyleneglycol(PEG)-modified liposomes for oral vaccine:effect of lipid dose on systemic and mucosal immunity[J].Journal of controlled release,2003,89:189-197.
[40] Jun-Mei Zhang.Effect of Amphipathic PEG-PE on the Circulation Time of Liposomes in vivo[J].Journal of Chinese Pharmaceutical Sciences,1996,5(2):111.
[41]李先红,李国栋.聚乙二醇包覆的醋酸泼尼松龙纳米脂质体的制备及性能研究[J].襄樊学院学报,2006,27(2).
[42]李慧良,高申,陈建民等.维生素A神经酰胺脂质体的初步研究[J].日用化学品科学,2007,30(9):15-17.
[43] Sophia Hatziantoniou,loannis P.Nezis,Lukas H.Margaritis,etc.Visualisation of liposomes prepared from skin and stratum corneum lipids by transmission electron microscopy[J].micron,2007,38(8):777-781.
[44]穆筱梅.聚乙烯醇修饰维生素E脂质体的制备及性质研究[J].香料香精化妆品,2007,12(6):23-25.
[45]曾翔云.维生素C的生理功能与膳食保障[J].中国食物与营养,2005,4:52-54.
[46]任欢鱼,韦异,朱海洋.维生素在皮肤护理中的应用[J].公司专栏,2004,11(15):40-42.
[47]裘炳毅.化妆品化学与工艺技术大全[M].北京:中国轻工业出版社,1997.629-630.
[48]章苏宁.化妆品工艺学[M].北京:中国轻工业出版社,2007.197-198.
[49] Elizabeth A.Offord,Jean-Charles Gautier,Ornella Avanti,etc.Photoprotective potential of lycopene,β-carotene,vitamin E,vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts[J].Free Radical Biology and Medicine, 2002, 32(12): 1293-1303.
[50] Ntei Abudu,James J.Miller,Mohammed Attaelmannan,etc.Vitamins in human arteriosclerosis with emphasis on vitamin C and vitamin E[J]. Clinica Chimica Acta, 2004,339(1-2):11-25.
[51] Ahmed S.Guinedi, Nahed D.Mortada, Samar Mansour,etc.Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide[J]. International Journal of Pharmaceutics,2005,306(1-2):71-82.
[52]杜美菊,王亚婷,赵凤林等.非离子表面活性剂囊泡对头孢菌素药物的缓释作用[J].化学研究,2005,16(3):67-70.
[53]赵晓宇,李慧,张保献.新型药物载体非离子囊泡的制备和评价研究进展[J].国际药学研究杂志,2007,34(6):439-443.
[54] Rita Cortesi,Elisabetta Esposito,Francesca Corradini,etc.Non-phospholipid vesicles as carriers for peptides and proteins:Production,characterization and stability studies[J]. International Journal of Pharmaceutics,2007,339(1-2):52-60
[55] Yongmei Hao,Fenglin Zhao,Na Li,etc.Studies on a high encapsulation of colchicines by a noisome system[J]. International Journal of Pharmaceutics,2002,244(1-2):73-80.
[56] Maria Manconi, Chiara Sinico, Donatella Valenti,etc. Niosomes as carriers for tretinoin: III. A study into the in vitro cutaneous delivery of vesicle-incorporated Maria Manconi, Chiara Sinico [J].International Journal of Pharmaceutics,2006,311(1-2): 11-19.
[57] Julijana Kristl,Breda Volk,Mirjana Gasperlin,etc.Effect of colloidal carriers on ascorbyl palmitate stability[J]. European Journal of Pharmaceutical Sciences,2003,19(4):181-189.
[58]龚盛昭.天然活性化妆品的概况和发展前景[J].香精香料化妆品,2002,4(2):16-19.
[59] A.Manosroi,K.Podjanasoonthon,J.Manosroi.Development of novel topical tranexamic acid liposome formulations[J]. International Journal of Pharmaceutics,2002,235:61-70.
[60]张蓓,王东凯,刘淑平等.硫酸多粘菌素E脂质体的制备及含量和包封率的测定[J].药物分析杂志,2005,25(8):920-923.
[61]王玉梅,郭桥,李秀芝等.干扰素脂质体的制备及理化性质分析[J].中国生物制品学杂志,2005.18(2):141-142.
[62]段逸松,张志荣.米托蒽醌脂质体制备工艺的研究[J].华西药学杂志,2001,16(2):91-92.
[63] Alma Foco,Mirjana Gasperlin,Julijana Kristl.Investigation of liposomes as carriers of sodium ascorbyl phosphate for cutaneous photoprotection[J]. International Journal of Pharmaceutics,2005,291:21-29.
[64]姜素芳,姚瑶,丁燕飞等.反相高效液相色谱法测定盐酸青藤碱纳米脂质体药物含量及包封率[J].中南药学,2005,3(4):213-216.
[65]穆筱梅,钟振声,陈焕钦.果酸脂质体的制备、检测及应用[J].香精香料化妆品,2002,5:25-27.
[66]王岩,周莉玲.青藤碱脂质体的制备及稳定性研究[J].中成药,2005,25(7):757-760.
[67]汪怡芳.半胱胺脂质体的研制[D]:[硕士学位论文].江苏:江南大学,2001.
[68]周国仪,舒静,黄泽元.响应面法优化超声提取芝麻叶黄酮的研究[J].食品与机械,2007, 23(3):77-80.
[69]袁超,金征宇.响应面法优化羟丙基-β-环糊精制备工艺[J].食品科学,2007,28(3):147-151.
[70] Mahesh N.Padamwar,Varsha B.Pokharkar.Development of vitamin loaded topical liposomal formulation using factorial design approach:Drug deposition and stability[J]. International Journal of Pharmaceutics,2006,320:37-44.
[71]吴有炜.试验设计与数据处理[M].苏州:苏州大学出版社,2002.135-143.
[72]余旭亚,赵声兰,李涛等.仙人掌SOD脂质体的制备研究[J].昆明理工大学学报,2002,27(1):103-105.
[73]郭海燕,莫穗林.脂质体物理稳定性和包封率的影响因素[J].中国新药杂志,2004,13(6):498-501.
[74]穆筱梅.聚乙烯醇修饰脂质体的制备研究[D]:[博士学位论文].广州:华南理工大学,2004.
[75]阮征,胡筱波,赖富饶等.油菜花粉中黄酮类物质提取工艺的优化研究[J].食品科学,2007,28(7):133-137.
[76]高静,姜艳军,周丽亚等.维生素C乳酸酯酶催化合成的相应曲面分析[J].精细化工,2006,23(9):916-920.
[77]陈钢,陈红兰,苏伟等.响应面分析法优化黄精多糖提取工艺参数[J].食品科学,2007,28(7):198-201.
[78] Martin C Woodle,Danile D Lasic.Sterically stabilized liposome[J].Biochimica et Biophysica Acta,1992,1113:171-199.
[79] Maria H.A.Zanin,Iris C.L.Torriani,Ricardo L.Zollner,et al.Physical characterization of surface-modified liposomes by incorporation of gangliosides designed for immunotherapies[J]. Colloids and Surfaces A: Physicochem.Eng.Aspects, 2004,251:175-182.
[80] Olga Garbuzenko,Yechezkel Barenholz,Aba Priev.Effect of grafted PEG on liposome size and on compressibility and packing of lipid bilayer[J]. Chemistry and Physics of Lipids,2005,135:117-129.
[81]史向阳,孙曹民,吴世康.胶原、壳聚糖包覆的小单层脂质体的体外稳定性评价[J].生物物理学报,1998,14(4):635-641.
[82] Hirofumi Takeuchi,Hiromitsu Yamamoto,Toshitada Toyoda,etc.Physical stability of size controlled small unilameller liposomes coated with a modified polyvinyl alcohol[J]. International Journal of Pharmaceutics,1998,164:103-111.
[83]朱斌,许时婴,夏书芹.薄膜水化法制备辅酶Q10脂质体[J].食品与机械,2006,22(6):39-41.
[84] S.L.Law,K.J.Huang,H.Y.Chou.Preparation of desmopressin-containing liposomes for intranasal delivery[J].Journal of control release,2001,70:375-382.
[85]孙京新,周光宏,徐幸莲.猪肉微粒体脂肪酸氧化产物对氧合肌红蛋白氧化的影响[J].南京农业大学学报,2004,27(1):101-104.
[86]陈涛,王昭,傅经国等.聚乙二醇修饰脂质体研究[J].世界最新医学信息文摘,2003,2(5):801-805.