全反式维甲酸前体脂质体的制备及体外评价

目的:制备维甲酸前体脂质体,并对其体外性质进行考察。方法:采用乙醇注入结合冷冻干燥法制备前体脂质体;微柱离心-高效液相色谱法测定脂质体的包封率;并进一步对其粒径、Zeta电位、血浆释放率及乙醇残留量进行测定。结果:所制备的前体脂质体包封率为95.2%,Zeta电位为-(28.4±17.5)mV,粒径为(170±29)nm,乙醇残留量为3.98%。结论:乙醇注入结合冷冻干燥法制备的维甲酸前体脂质体包封率高,粒径均匀,稳定性好。     

槲皮素前体脂质体的质量考察

目的制备液体型槲皮素前体脂质体,并对制剂质量进行考察。方法采用一种新型前体脂质体制备方法制备液体型槲皮素前体脂质体,将脂质体膜材和药物等以一定比例溶于分散介质中,形成一种无水的澄明溶液。考察其水合后粒子形态、粒径、电位、包封率及自组装速度等理化性质,并评价其体外释药性质。结果槲皮素前体脂质体遇水即可快速自组装成纳米级含药脂质体混悬液,水合后形态多为类球形,平均粒径为228.7nm,Zeta电位为21.2 mV,包封率可达90%以上,体外释药符合Higuchi方程。结论槲皮素口服前体脂质体制备工艺简单可行,包封率高,具有一定的缓释效果。     

葛根素前体脂质体的质量考察

目的:制备葛根素前体脂质体,并对制剂质量进行考察。方法:采用山梨醇载体沉积法制备葛根素前体脂质体,并对制剂的形态学、包封率、粒径分布、体外释药、稳定性等性质进行考察。结果:本实验制备的脂质体形态多为圆形或椭圆形,平均粒径为278nm,Zeta电位为-17.5mV,包封率为(43.5±1.3)%,体外释药符合一级动力学方程,常温放置稳定。结论:葛根素前体脂质体包封率较高,具有一定的缓释效果,稳定性较好。     

洛伐他汀脂质体的制备及表征

目的：研制洛伐他汀脂质体,考察其制备的影响因素,优化处方工艺,并对其特性进行表征。方法：采用薄膜分散法制备洛伐他汀脂质体,以包封率、粒径和Zeta电位为指标参数,考察表面活性剂、水合介质及药脂比对其制备的影响;并评价其理化性质及稳定性。结果：以脱氧胆酸钠-泊洛沙姆188（1∶2）为表面活性剂、去离子水为水合介质和药脂比为1∶40制备的洛伐他汀脂质体具有最佳的包封率（〉90%）、粒径（90～110 nm,分布系数为0.32）和Zeta电位（-35～-39 mV）;其外观圆整,内部具指纹状结构;在4℃下放置30 d,包封率、粒径及Zeta电位均无明显变化。结论：采用薄膜分散法制备的洛伐他汀脂质体具有良好的理化特性及稳定性。     

尼莫地平前体脂质体的制备及其质量评价

目的制备尼莫地平前体脂质体,并进行质量评价,以期得到高效、低毒和稳定的尼莫地平新剂型。方法采用叔丁醇-水共溶剂冻干法制备尼莫地平前体脂质体,考察了影响药物包封率的因素,并对重建脂质体的药物含量、包封率、粒径、Zeta电位、溶血性及稳定性进行考察。结果磷脂浓度、表面电荷是影响尼莫地平脂质体包封率的主要因素。尼莫地平脂质体包封率大于98%,平均粒径为57 nm,Zeta电位小于-20 mV,无溶血性,稳定性好。结论采用叔丁醇水共溶剂冻干法获得了高包封率、粒径均一、无溶血性、稳定的尼莫地平前体脂质体制剂,可用于静脉注射给药。     

薄膜分散法制备白藜芦醇长循环热敏前体脂质体及其表征研究

目的:对白藜芦醇长循环热敏前体脂质体制备的研究以及对其性质进行分析。方法:先用薄膜分散法制备白藜芦醇长循环热敏脂质体后,再用冷冻干燥法来制备白藜芦醇长循环热敏脂质体的前体。采用电势测定仪、HPLC等方法对该脂质体的包封率、粒径、稳定性、载药量、电位、释放度等来展开系统的检查。结果:白藜芦醇长循环热敏前体脂质体水合后形成白藜芦醇长循环热敏脂质体,粒径均值为(107.9±3.6)nm,Zeta电位的均值为(-12.2±1.6)m V,包封率可达89.4%;该脂质体在相变温度42℃下药物释放达到94%以上。结论:采用长循环热敏来制备的白藜芦醇前体脂质体含量与包封率检查方法准确、快速、简单且方法简便易行。载药量大,包封率好,工艺比较稳定。本实验可为新型白藜芦醇静脉注射用热敏脂质体的研究提供基础。     

紫杉醇长循环热敏前体脂质体的制备与表征

目的:研究紫杉醇长循环热敏前体脂质体的制备并对其性质进行考察.方法:采用薄膜分散法制备紫杉醇长循环热敏脂质体,再用冷冻干燥技术制备紫杉醇长循环热敏前体脂质体;采用激光粒度仪考察粒径和Zeta电位;采用高效液相色谱法研究其含量与包封率;并考察脂质体的体外释药特性.结果:紫杉醇长循环热敏前体脂质体水合后形成紫杉醇长循环热敏脂质体,粒径均值为(108.6 ±3.6)nm,Zeta电位的均值为(-12.2±1.8)mV,包封率可达96.2％;该脂质体在相变温度42℃下药物释放达到95％以上.结论:紫杉醇长循环热敏前体脂质体的制备工艺稳定,载药量大,包封率高,具有良好的热敏性;含量及其包封率测定方法简单、快速、准确.本实验可为紫杉醇静脉注射用新制剂的开发提供研究基础.     

依托泊苷长循环热敏前体脂质体的制备工艺研究

目的:对依托泊苷(Etoposide,VP-16)长循环热敏前体脂质体的制备工艺进行研究,并对该制备工艺进行方法学及制剂质量考察。方法:应用薄膜分散法制成VP-16长循环热敏脂质体,进一步借助冷冻干燥技术进行依托泊苷长循环热敏前体脂质体的制备;采用zeta电势测定仪及HPLC等技术进行方法学考察,主要包括脂质体的包封率、粒径、载药量、电位、释放度、稳定性。结果:VP-16长循环热敏前体脂质体水合形成长循环热敏脂质体,粒径为(105.2±3.4)nm,Zeta电位为(-11.9±1.7)m V,包封率可达96.8%;该脂质体在相变温度42℃下药物释放达到96%以上。结论:VP-16长循环热敏前体脂质体的制备工艺稳定,脂质体载药量大,包封率高;药物含量及包封率的测定方法简单、快速而准确,因而,该研究可为VP-16开发成静脉注射用新制剂提供数据支持。     

羟基喜树碱脂质体的制备及质量评价研究

目的:制备羟基喜树碱(HCPT)脂质体,并对其质量进行评价.方法:采用薄膜分散-高压乳匀法制备羟基喜树碱脂质体;用激光粒度分析仪测定其Zeta电位、粒径大小;考察其在0.9%NaCl溶液、水、5%葡萄糖溶液中8 h的稳定性;用凝胶柱层析法考察包封率;采用薄膜透析法考察体外释药性质.结果:羟基喜树碱脂质体Zeta电位为(-33.1±1.3) mV,平均粒径(182.5±5.6) nm,8 h内在水、5%葡萄糖溶液中稳定性良好;包封率(91.2±1.2)%;体外释药曲线符合Higuchi方程Q=1.291 6t1/2 0.309 8,r=0.980 3.结论:本试验制备的羟基喜树碱脂质体稳定性好,大小均匀, 包封率高,并具有延缓药物释放的性质.     

两亲性壳聚糖包覆紫杉醇脂质体的制备及体外释放研究

目的:制备两亲性壳聚糖N-辛基-N,O-羧甲基壳聚糖包覆紫杉醇脂质体(PTX-LP-OCC),并考察其理化性质及体外释放行为。方法:采用基于乙醇的前体脂质体法制备紫杉醇脂质体并以OCC包覆,并以普通脂质体(PTX-LP)为对照,测定其包封率、粒径大小、电位,观测其形态及稳定性,然后采用全体液平衡反向透析法研究体外释放行为。结果:紫杉醇脂质体包封率为89.5%,粒径为236.5 nm,Zeta电位为-31.4 mV,多糖包覆修饰后药物包封率无显著变化,粒径及Zeta电位显著增加,脂质体稳定性显著提高,药物释放呈缓释特征,且突释显著降低。结论:两亲性壳聚糖包覆脂质体是一个有前景的抗肿瘤药物递送载体     

依托泊苷隐形前体脂质体的构建及家兔体内药动学研究

构建依托泊苷隐形前体脂质体，并考察其在家兔体内的药动学。采用薄膜分散法构建窄白隐形脂质体；硫酸铵梯度法包封依托泊苷；结合真空冷冻干燥技术构建依托泊苷隐形前体脂质体。采用凝胶色谱法测定脂质体包封率；透射电镜观察脂质体的形态；电泳光散射技术测定Zeta电位与粒径分布；以市售依托泊苷注射液和普通脂质体为参比制剂，评价其在家兔体内药动学特点。脂质体平均包封率为83．92％±3．65％，粒径为（124．5±26．9）nm，Zeta电位为（-39．50±1．04）mV，家兔单剂量静脉注射1．5mg／kg依托泊苷制剂后呈二室模型特征，依托泊苷隐形前体脂质体的T1/2β为（19．26±3．16）h，AUC为（26．04±3．53）μg／h／mL；注射液的T1/2β为（0．94±0．21）h，AUC为（0．98±0．26）μg／h／mL；普通脂质体的T1/2β为（7．99±1．36）h,AUC为（11．65±1．70）μg/mL。构建的隐形前体脂质体包封率高，且延长了依托泊苷在血液中的循环时间。     

2-甲氧基雌二醇脂质体的质量评价

目的:对2-甲氧基雌二醇(2-ME)脂质体进行质量评价. 方法:用乙醚注入法制备2-ME脂质体,与原料药相比,体外释药情况的考察. 并从粒径包封率两个方面进行稳定性考察. 结果:体外释药试验表明,与原料药相比,脂质体无突释现象且持续释药, 4℃存放两周稳定性较好. 结论:用乙醚注入法制备的2-ME脂质体质量稳定,可为2-ME的临床应用提供一种新剂型.     

Preparation and evaluation of N(3)-O-toluyl-fluorouracil-loaded liposomes

This study was aimed at developing a liposome delivery system for a new and potential antitumor lipophilic prodrug of 5-fluorouracil (5-Fu)-N(3)-O-toluyl-fluorouracil (TFu), intended to improve the bioavailability and therapeutic efficacy of 5-Fu by oral and intravenous administration. TFu-loaded liposomes were prepared by a modified film dispersion-homogenization technique, the formulation and manufacture parameters were optimized concerning the drug encapsulation efficiency. TFu-loaded liposomes were characterized according to particle size, size distribution, zeta potential, drug entrapment efficiency, drug loading and physical stability, respectively. In vitro release characteristics, in vivo pharmacokinetic properties and bioavailabilities were also investigated. The formulated liposomes were found to be relatively uniform in size (400.5 +/- 9.6 nm) with a negative zeta potential (-6.4 +/- 0.8 mV). The drug entrapment efficiency and loading were (88.87 +/- 3.25%) and (8.89 +/- 0.19%), respectively. The physical stability experiments results indicated that lyophilized TFu-loaded liposomes were stable for at least 9 months at 4 degrees C. In vitro drug release profile of TFu-loaded liposomes followed the bi-exponential equation. The results of the pharmacokinetic studies in mice indicated that the bioavailability of TFu-loaded liposomes was higher than the suspension after oral administration, and was bioequivalent comparing with TFu 50% alcohol solution after intravenous (i.v.) administration. These results indicated that TFu-loaded liposomes were valued to develop as a practical preparation for oral or i.v. administration.     

N-三甲基壳聚糖包衣的盐酸阿霉素脂质体的制备

研制N-三甲基壳聚糖（TMC）包衣的盐酸阿霉素（ADM）脂质体。方法：采用硫酸铵梯度法制备ADM脂质体,以包封率为指标,筛选盐酸阿霉素脂质体最佳处方;合成不同季铵化程度的TMC,并对最佳ADM脂质体进行包衣。结果：未包衣ADM脂质体平均粒径为（378．6±5．2）nm,Zeta电位为（-62．08±2．5）mv,平均包封率为（62．27±1．75）％（n=3）。TMC包衣后,脂质体粒径增大,并随着TMC季铵化程度的增大,Zeta电位显著增大（p＜0．05）;TMC20、TMC40、TMC60包衣脂质体体外释药曲线符合Higuchi方程,分别为：Q=7．6315＋3．7863t1／2（r=0．9292）,Q=6．9647＋3．5709t1／2（r=0．9318）,Q=7．3451＋2．7665t1/2（r=0．9357）。结论：TMC包衣ADM脂质体的制备工艺可行,其表面带有较高正电性,为下一步研究其血管靶向性打下基础。     

pH梯度法结合逆向蒸发法制备氟尿嘧啶脂质体

目的：以pH梯度法结合逆向蒸发法制备氟尿嘧啶脂质体,并评价其质量。方法：采用pH梯度法结合逆相蒸发制备氟尿嘧啶脂质体,以包封率为指标进行处方优化;用Sephadex G-50葡聚糖凝胶柱分离-高效液相色谱法测定氟尿嘧啶脂质体的包封率;以激光散射粒径分析仪测定脂质体的平均粒径及Zeta电位,透射电镜观测形态,并初步考察脂质体在室温和4℃冷藏条件下的稳定性。结果：制得的氟尿嘧啶脂质体外观形态圆整,平均粒径为282nm,Zeta电位为-25．9mV,平均包封率为75．39％,4℃冷藏条件下贮存脂质体的稳定性要明显优于室温贮存。结论：运用pH梯度法结合逆向蒸发法能制备包封率较高的氟尿嘧啶脂质体。     

米诺地尔醇脂质体的制备

目的制备米诺地尔醇脂质体并评价其质量。方法采用乙醇注入法制备米诺地尔醇脂质体,以包封率为评价指标进行正交试验筛选出最佳的处方和工艺。采用HPLC测定主药含量、透析袋法测定醇脂质体的包封率。并对其粒径、电位、包封率等理化性质进行研究。结果各因素最佳的水平组合：药脂重量比为1∶10、胆固醇与大豆磷脂的重量比为1∶2、无水乙醇为处方量的30%。所制醇脂质体为乳黄色,平均粒径为1.103μm,Zeta电位为-3.69 mV,平均包封率为66.7%。结论米诺地尔醇脂质体的制备工艺简便可行,质量稳定可控,为开发新剂型奠定了实验基础。     

Melittin liposomes surface modified with poloxamer 188: in vitro characterization and in vivo evaluation

Melittin liposomes surface modified with poloxamer 188 were developed, and the effect of poloxamer 188 was investigated with regard to anti-cancer effect and vascular stimulation. Melittin liposomes surface modified with poloxamer 188 at different concentrations (0%, 2%, and 5%) were prepared using the adsorption method, followed by in vitro characterization, including entrapment efficiency, zeta potential, particle size, and morphology. Subsequently, the influence of repeated freeze-thawing on the liposomes was investigated, and the effect of poloxamer 188 on the repeated freeze-thawing process was explored. Vascular stimulation effects of MLT, and MLT liposome that surface coated with or without poloxamer were all studied. Pharmacokinetics of the different MLT preparations were determined and the anticancer activity of the MLT formulations was investigated. The particle size of the liposomes gradually increased with increasing poloxamer 188 content, while the entrapment efficiency did not change significantly. After the first freeze-thaw cycle, size and PDI were both markedly reduced, entrapment efficiency rose, and there was no significant change of zeta potential. The vascular irritation caused by MLT could be reduced to an extent by encapsulation in liposome, but not completely eliminated, while liposomes coated with poloxamer 188 can effectively abolish the phenomenon. Melittin liposomes with surface modified by poloxamer exhibit enhanced bioavailability, effective anticancer activity, and reduced side effects compared with melittin solution. Poloxamer plays an important role in melittin liposomes.     

2种方法制备银杏内酯长循环固体脂质纳米粒的比较

目的:研究银杏内酯AB长循环固体脂质纳米粒(GAB-LSLN)的制备方法,并探讨GAB-LSLN的主要理化性质。方法:分别采用超声法和高压乳匀法制备GAB-LSLN。在电镜下观察其形态,测定其粒径、Zeta电位和包封率,并在室温下放置4周,观察GAB-LSLN的稳定性。结果:超声法制备的GAB-LSLN在透射电镜下呈片状存在,形态不规则;高压乳匀法制备的GAB-LSLN呈球状,形态规则。超声法和高压乳匀法制备的GAB-LSLN粒径分别为(219.6±14.3)nm和(173.9±10.4)nm(P<0.001);Zeta电位分别为(—21.12±1.03)mv和(—27.43±2.14)mV(P<0.001),包封率分别为(85.05±0.67)%和(92.49±0.88)%(P<0.001)。高压乳匀法制备的GAB-LSLN室温放置4周后,粒径无显著增加(P>0.05)。结论:高压乳匀法制备GAB-LSLN具有粒径小、稳定性和包封率高的特点,优于超声法。