主动靶向脂质体的相变温度与靶细胞摄取的相关性研究

分别采用二硬脂酰磷脂酰胆碱(DSPC)、氢化大豆磷脂(HSPC)、二棕榈酰磷脂酰胆碱(DPPC)和二肉豆蔻酰磷脂酰胆碱(DMPC)为载体,制备了NGR肽(Asn-Gly-Arg)修饰的主动靶向脂质体,并用其负载香豆素-6.结果表明,4种脂质体的粒径为120～160 nm,粒度分布均匀,ζ电位接近中性,包封率均在95％以上.差示扫描量热分析(DSC)表明,4种脂质体的相变温度(Tm)值由高至低分别为DSPC脂质体＞HSPC脂质体＞DPPC脂质体＞DMPC脂质体.以CD13高表达的HT1080细胞为模型,采用流式细胞仪、激光共聚焦显微镜观察评价脂质体的入胞效果.结果显示,脂质体的入胞效率与Tm值呈正相关.     

药物载体——脂质体

近年来磷脂赋形剂——脂质体(Liposome)已成功地用作药物运载赋形剂,在降低细胞毒性、方便使用和具有多种特点供不同用途方面它都优于聚合物或微型胶囊。脂质体是能将药物包封在双层磷脂的碟状液晶分子(Smetic)的中间而制成的有机物。最常用的磷脂为:蛋磷脂酰胆碱、合成二棕榈酰-DL-α-磷脂酰胆碱、脑和合成磷脂酰丝氨酸、(神经)鞘磷脂、磷脂酰肌醇和卵磷脂。脂质体在结构上主要可分为三类:(1)多层状或多房室脂质体,为不均匀的聚集体,各含有被水分子隔开的几层磷脂;(2)单房室脂     

磷脂酰乙醇脂质体作为胰岛素口服给药载体在大鼠体内的研究

脂质体作为一种磷脂载体是体内可生物降解的无毒载体 ,可以包封亲水性及疏水性药物 ,药物包裹其中能防止酶降解和免疫系统的识别。近年来有关胰岛素脂质体制剂的研究日益增多。脂质体中胰岛素的降血糖活性与类脂的组成、表面电荷以及磷脂双层的物理状态有关。灌胃给予包封胰岛素的高熔点二棕榈酰磷脂酰胆碱 (ＤＰＰＣ)脂质体或荷负电的磷脂酰肌醇 (ＰＩ)脂质体 ,血糖浓度显著降低。本文对以高熔点荷负电的二棕榈酰磷脂酰乙醇 (ＤＰＰＥ)为膜材的胰岛素脂质体制剂进行研究。实验应用ＤＰＰＥ为膜材制备脂质体 ,并考察了包封胰岛素的脂质体在…     

鬼臼毒素二棕榈酰磷脂酰胆碱前体脂质体的制备及初步实验研究

目的研制鬼臼毒素二棕榈酰磷脂酰胆碱前体脂质体(PPT-DPPC-PL),提高鬼臼毒素二棕榈酰磷脂酰胆碱脂质体(PPT-DPPC-L)的稳定性.方法采用冷冻干燥法,选择海藻糖做冻干剂制备PPT-DPPC-PL,并观察乳猪局部外用PPT-DPPC-L及重建型PPT-DPPC-L(R-PPT-DPPC-L)后血药浓度的变化.结果 PPT-DPPC-PL呈疏松、洁白的粉末状.二种PPT-DPPC-L经局部外用后动物体内血药浓度均值无显著统计学差异,血药浓度趋势基本一致.结论 R-PPT-DPPC-L与PPT-DPPC-L有一致的透皮吸收率.冷冻干燥法不会破坏PPT-DPPC-L的稳定性,不会改变机体对PPT-DPPC-L的透皮吸收特性.     

新型阿霉素热敏脂质体的研制

目的:探讨以二棕榈酰磷脂酰胆碱(DPPC)和单棕榈酰磷脂酰胆碱(MPPC)为原料制备的温度敏感阿霉素脂质体的制备工艺和理化性质.方法:采用膜过滤挤压法和pH梯度法制备阿霉素脂质体,以紫外分光光度法检测样本中阿霉素含量,计算阿霉素热敏脂质体在不同温度下的药物释放特性,并对其包裹率、粒径,pH值进行研究.结果:阿霉素热敏脂质体在39℃下迅速释放,前20 s内释放药物50%,42℃下药物释放达到60%以上.包封率99.5%,平均粒径90.8 nm,pH值为6.5.结论:制备的热敏感阿霉素脂质体优于常规脂质体,具有良好的温度控释特性.     

维生素B_(12)脂质体的制备及体外释放

由于抗恶性贫血药维生素B_(12)是在肝脏中贮藏,而脂质体具有靶器官定向作用的独特优点,因而设想以脂质体给药可以减少剂量并收到较好的效果。用维生素B_(12)盐酸盐分别与合成类脂L-α二棕榈酰磷脂酰胆碱(DPPC)和L-α二肉豆蔻酰磷脂酰胆碱(DMPC)制成脂质体,制备时或加进磷酸二鲸蜡酯或硬脂酰胺使脂质体带上负电或正电荷。具体制法是将10~(-4)M类脂,其中包括10%(克分子百分比)荷电物质置于圆底烧瓶内,以25ml氯仿溶解,在旋转蒸发器上于48°真空蒸发至呈干燥薄层。然后加进含50mgB_(12)、pH为7.0的0.01M磷酸盐缓冲液25ml,缓缓搅动,形成B_(12)的多层脂质体。将混悬液于4～6°放置96小时以保证类脂充分水合,离心后分散于磷酸盐缓冲液中,再经离心即得。     

HPLC-ELSD法测定复方氟尿嘧啶注射液中磷脂酰胆碱的含量

目的 建立测定复方氟尿嘧啶注射液中磷脂酰胆碱含量的方法.方法 用硅胶为填充剂,采用梯度洗脱程序,在蒸发光检测器下分析测定脂质体中磷脂酰胆碱的含量.结果 在50～400 μg·mL-1范围内,磷脂酰胆碱对照品的峰面积与浓度呈良好的线性关系(r＝0.9958),平均回收率为99.7％ (RSD＝0.9％).结论 本法用于测定磷脂酰胆碱的含量快速、简便、重复性好.     

盐酸小檗碱脂质体的制备及体外释放度测定

用硫酸铵梯度法制备高包封率（8（％以上）的小檗碱脂质体注射液.采用氢化磷脂酰胆碱以避免产生溶血性磷脂酰胆碱.优化后的处方：氢化磷脂酰胆碱-胆固醇-培化磷脂酰乙醇胺的质量比为3∶1∶1.制成的注射剂具有缓释和长循环功效.     

从脂质体两性霉素B中分离两性霉素B的固相萃取法

两性霉素B是重要的抗霉菌抗生素,为了减少其毒性,现采用与磷脂(二肉豆蔻酰磷脂酰胆碱DMPC和二肉豆蔻酰磷脂酰甘油DMPG)结合成脂质体两性霉素B。脂质体两性霉素B制剂含有5mg/ml两性霉素B和6.5mg/ml类脂体(7ml DMPC和3 mlDMPG)于生理盐水中。由于类脂体的干扰使微生物法测定两性霉素B效价结果偏低,因此在测定前需将类脂体预先分离除去,常规的萃取方法分离类脂体的效果不佳,从TLC实验表明,硅胶板用氯仿:甲醇:丙酮:水:氨水(65∶30∶5∶2∶2)展开时二个类脂体和药物之间的迁移行为有较大差别,提示可用硅胶     

用差示扫描量热法及激光拉曼光谱研究足叶乙甙对二棕榈酰磷脂酰胆碱脂质体膜流动性影响

本文用DSC和激光拉曼光谱研究抗癌药物足叶乙甙(4-去甲基表鬼臼毒素-β-D-乙叉吡喃葡萄糖甙,简称VP 16-213)与二棕榈酰磷脂酰胆碱(DPPC)脂质体的作用。VP 16-213分子掺入DPPC脂质体双层中,不但使相转变温度向高温移动,而且吸热峰的半高宽度随VP 16-213浓度增加而变宽。其Raman光谱在频率2850 cm~(-1)处的C-H键对称伸缩振动亦随着药物浓度增加而减弱。这些结果表明VP 16-213分子是定域在脂双层中DPPC分子链的C_1～C_9亚甲基区域,使脂质体的有序性提高而流动性降低。     

Preparation of novel double liposomes using the glass-filter method

The glass-filter method, a newly developed preparative method for liposomes, was applied for preparation of novel double liposomes. Double liposomes were prepared by filtering a suspension of liposomes prepared using a G4 filter (pore size: 10-16 microm) into a G3 filter (pore size: 40-100 microm) coated with a similar lipid layer. The morphological structure of the double liposomes was confirmed using scanning electron microscopy by the freeze-fracture method to be multivesicular vesicles consisting of small liposomes enveloped in larger liposomes. The diameter of liposomes prepared using the G4 filter was 0.8-2 microm and that of liposomes prepared using the G3 filter or double liposomes was 5-10 microm. These results suggested that the particle size of liposomes is dependent on the pore size of the glass-filter. The encapsulation efficiencies of double liposomes for brilliant blue FCF (BB) and erythrosine (ER) were higher than those of liposomes prepared by the standard Bangham method. Double liposomes showed suppressed release of BB or ER compared with normal liposomes. In particular, no release of BB was observed from the double liposomes prepared with stearylamine. These findings implied that the outer lipid layer protects the inner liposomes. The glass-filter method is the only method that we can get the double liposomes in a short period, and double liposomes prepared by this novel method had adequate size and good stability in vitro.     

米非司酮脂质体的制备及性质考察

目的研制米非司酮脂质体。方法采用薄膜分散法制备米非司酮脂质体,应用葡聚糖凝胶法测定包封率,并考察该脂质体的形态、粒径、稳定性和体外释放特性。结果所制备的米非司酮脂质体包封率达85．2％,平均粒径为112．7nm,4℃冷藏保存3个月稳定性良好,具有体外缓释作用。结论米非司酮脂质体制备工艺简单可行,脂质体制剂学性质稳定。     

磷脂组成对马钱子碱脂质体在大鼠体内药物动力学的影响

分别以氢化大豆磷脂(HSPC)和大豆磷脂(SPC)为膜材,采用硫酸铵梯度法制备了马钱子碱脂质体.考察了两种不同磷脂组成脂质体在体外的释放度和大鼠体内的药物动力学行为.HSPC脂质体在大鼠血浆中的稳定性较SPC脂质体显著提高.大鼠体内试验表明,HSPC脂质体中马钱子碱的AUC_(0-t),是SPC脂质体的3.6倍,而MRT、V_(ss)仅为后者的37%和13%.     

A study of stabilization effect of α-tocopherol incorporated into liposomal phospholipid membrane

The stabilization effect of α-tocopherol incorporated into liposomal phospholipid membrane was investigated by fluorospectrophotometry and UV-visible spectrophotometry. The release of entraped carboxyfluorescein from liposomes was markedly retarded by the presence of α-tocopherol in the bilayer of liposomal phospholipid membrane relative to cholesterol-containing liposomes and pure phospholipid liposomes. α-tocopherol-containing liposomes prolonged the oxidation of liposomes-embedded heme as an oxygen carrier. The oxidation index of α-tocopherol-containing liposomes was lower than those of cholesterol-containing liposomes and pure phospholipid liposomes. Thus α-tocopherol-containing liposomes may be useful for the carrier systems of nutrients and drugs to phospholipid bilayer and stabilized liposomes.     

新型脂质体的研究进展

作为药物传递系统的载体,几种新型脂质体如膜融合脂质体、柔性脂质体、表面修饰脂质体等的研究己取得显著进展.本文归纳和分析了近期有关脂质体稳定性、靶向性及修饰材料的文献.     

硫唑嘌呤脂质体的研制

目的 :优选硫唑嘌呤脂质体的处方和制备工艺 ,并评价其质量。方法 :采用薄膜 -振荡分散法制备硫唑嘌呤脂质体 ,以正交试验法优选出制备硫唑嘌呤脂质体的最佳工艺条件。用滴定法测其包封率 ,显微镜法观察其形态 ,测量粒径和粒度分布。结果 :制备的脂质体的包封率达到49 19 % ,透射电子显微镜下观察脂质体为粒径均匀的球状或近球状的多室脂质体 ,小于2 4μm的粒子占78 17 %。结论 :优选得到的脂质体处方和制备工艺合理、稳定     

大豆磷脂脂质载体与胆酸盐表面活性剂的体外相互作用

采用旋转薄膜蒸发法结合挤压过滤工艺制备大豆磷脂脂质体,所制得脂质体的平均粒径为217nm,跨距0．838,负染色脂质体经透射电镜观察,呈明显的双层膜圆球型结构。以胆酸钠盐和脱氧胆酸钠盐研究其与脂质体之间的相互作用,将500nm波长处的可见光吸收值评价胆盐-脂质体混悬液的浊度,测定脂质体的粒径变化情况。在胆酸盐加入的初期,由于胆酸盐和脂质体形成混合胶团,致使脂质体的粒径和浊度值稍有增加,进一步加入的胆酸盐使脂质体的粒径和浊度值下降。胆盐和脂质体问的相互作用经历了数个重排现象,使脂质体的粒径发生规律性的变化,这与脂质体的体内稳定性密切相关,也可反映脂质体的载药和释药特性。     

染料木黄酮脂质体的制备及其对肿瘤细胞体外增殖的抑制作用

目的研究染料木黄酮脂质体的制备方法及其对肿瘤细胞体外增殖的影响。方法采用超声薄膜法制备染料木黄酮脂质体;活细胞计数法和MTT法观察染料木黄酮脂质体对肿瘤细胞的增殖抑制作用。结果染料木黄酮脂质体的平均粒径为136．7nm,剂量依赖性抑制A549和HepG2细胞的增殖,IC50分别为10．46、12．34μmol／L。结论染料木黄酮脂质体对A549和HepG2肿瘤细胞有明显的增殖抑制作用,且作用强于游离染料木黄酮。     

氧化苦参碱脂质体的制备及其质量评价

目的:制备氧化苦参碱脂质体并建立其质量评价方法。方法:采用逆相蒸发法,以包封率为检测指标,利用正交试验法优选处方和制备工艺;考察优选处方所制脂质体形态与粒径,并采用透析法结合反相高效液相色谱法测定其包封率。结果:最佳处方为磷酸盐缓冲液pH7.2,大豆卵磷脂与胆固醇的质量比为2∶1,大豆卵磷脂与氧化苦参碱质量比为10∶1,水相与有机相体积比为1∶3;制备的脂质体为球状小囊泡,外观圆整,粒径范围60～150nm,包封率为60.72%;氧化苦参碱检测浓度线性范围为10～150μg.mL-1(r=0.9998),平均回收率为98.62%(RSD=1.47%,n=5)。结论:优选处方和制备工艺稳定可行,可为开发其新剂型提供参考。     

Physicochemical properties and antioxidant activity of gamma-oryzanol-loaded liposome formulations for topical use

The objective of this study is to prepare the γ-oryzanol-loaded liposomes and investigate their physicochemical properties and antioxidant activity intended for cosmetic applications. Liposomes, Composing phosphatidylCholine (PC) and Cholesterol (Chol), CHAPS or sodium taurocholate (NaTC) were prepared by sonication method. γ-oryzanol-loaded liposomes were prepared by using 3, 5 and 10% γ-oryzanol as an initial concentration. The formulation factors in a particular type and composition of lipid and initial drug loading on the physicochemical properties (i.e., particle size, zeta potential, entrapment efficiency, drug release) and antioxidant activity were studied. The particle sizes of bare liposomes were in nanometer range. The γ-oryzanol-loaded liposomes in formulations of PC/CHAPS and PC/NaTC liposomes were smaller than PC/Chol liposomes. The incorporation efficiency of 10% γ-oryzanol-loaded PC/Chol liposomes was less than γ-oryzanol-loaded PC/CHAPS liposomes and PC/NaTC liposomes allowing higher in vitro release rate due to higher free γ-oryzanol in buffer solution. The antioxidant activity of γ-oryzanol-loaded liposomes was not different from pure γ-oryzanol. Both γ-oryzanol-loaded PC/CHAPS liposomes and PC/NaTC liposomes were showed to enhance the antioxidant activity in NHF cells. γ-oryzanol-loaded PC/Chol liposomes demonstrated the lowest cytotoxicity in NHF cells. It was conceivably concluded that liposomes prepared in this study are suitable for γ-oryzanol incorporation without loss of antioxidant activity.