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。     

洛伐他汀自组装前体脂质体的制备及其理化性质的研究

目的:为研究洛伐他汀新剂型,制备洛伐他汀新型前体脂质体,并对其质量进行考察。方法:采用一种新型前体脂质体制备方法将洛伐他汀制成自组装前体脂质体,对水合后脂质体的形态、粒径、Zeta电位、包封率、自组装速度、稳定性等进行考察,验证这种新型前体脂质体制备方法用于制备洛伐他汀脂质体的可行性。结果:所形成的洛伐他汀脂质体包封率为95.4%±6.7%,平均粒径为(327.4±29.6)nm,Zeta电位值为-(22.4±1.5)mV。洛伐他汀自组装前体脂质体可在60 s内自发形成脂质体并达到分散平衡;以人工胃液为稀释介质,洛伐他汀脂质体在12 h内稳定。结论:采用新型前体脂质体制备方法可将洛伐他汀制成洛伐他汀脂质体,形成的脂质体包封率较高且具有良好的稳定性。     

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     

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。     

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。     

辅酶Q10脂质体的制备及质量考察

目的制备辅酶Q10脂质体,并考察其性质.方法采用乙醇注入法制备辅酶Q10脂质体,正交设计优化处方,采用滤膜过滤分离-HPLC法测定脂质体包封率,并测定其Zeta电位和粒径,考察其稳定性.结果按正交设计最优组合制备的脂质体含药量为1.93 g·L-1,包封率为99.2%,Zeta电位为-31.2 mV,平均粒径为163 nm.结论乙醇注入法制得的辅酶Q10脂质体包封率高,粒径小而均一,稳定性较好.     

紫草素的脂质体制备工艺及其质量评价研究

目的:研究紫草素脂质体的制备方法及质量评价。方法:采用薄膜超声法制备紫草素脂质体,超速离心法测其包封率;以包封率、粒径为指标,采用正交试验设计法优化处方,并对其表面特征、包封率、粒径、Zeta电位进行考察。结果:优化处方制备的脂质体平均粒径为187.73 nm,药物的平均包封率为76.9%,Zeta电位绝对值为38.94 mV,外观圆整,分散均匀。结论:制备的紫草素脂质体包封率较高,粒径小,混悬液体系稳定,为紫草素脂质体的进一步研究奠定基础。     

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。     

尼莫地平鼻用冻干脂质体的制备及大鼠鼻黏膜吸收

采用改良乙醇注入法制备了尼莫地平脂质体，运用均匀设计试验优化了脂质体处方，并考察了冷冻干燥工艺与处方因素对其冻干脂质体性质的影响。在优化冻干工艺条件下，甘露醇和蔗糖合用为冻干保护剂，可得到外观良好、易于重建的冻干脂质体，冻干前后的药物包封率分别为97．1％和96．2％，粒径分别为175．1nm和227．9nm。-20℃及4℃贮存3个月，粒径和包封率无显著变化。采用大鼠在体鼻腔循环灌流法，考察了尼莫地平鼻用脂质体及其冻干重建制剂的鼻黏膜吸收规律。结果表明不同药物浓度脂质体及冻干重建脂质体的鼻黏膜吸收速率常数K无显著性差异，药物吸收呈一级动力学特征。     

Development and pharmacokinetics of nimodipine-loaded liposomes

In order to improve the water solubility of nimodipine and prolong the time of the drug in the circulation, nimodipine-loaded liposomes with a small size and high entrapment efficiency were prepared by a method that was easy to scale up (the modified ethanol injection method). The nimodipine liposome dispersions were characterized with respect to particle size distribution, zeta potential and entrapment efficiency. Liposomal nimodipine and nimodipine solution were intravenously administered to mice as a single dose of 4 mg kg-1. The pharmacokinetic parameters of nimodipine changed significantly when encapsulated in liposomes. The clearance of nimodipine encapsulated in liposomes was reduced and the elimination half-life was prolonged. The ratios of the area under the curve values of nimodipine liposomes to nimodipine solution were 1.78 and 1.90 in plasma and cerebral tissue, respectively. The drug concentration in cerebral tissue and in plasma showed a good linear correlation, which showed that liposomes could efficiently deliver nimodipine into brain tissue. These findings suggest that intravenous administration of liposomal nimodipine produces higher and more stable plasma and cerebral drug concentrations compared with nimodipine solution. In conclusion, liposomal nimodipine is a promising alternative to the solution preparation.     

Preparation of silymarin proliposome: a new way to increase oral bioavailability of silymarin in beagle dogs

The aim of the present study was to find a method to increase oral bioavailability of silymarin, that is to say, by the preparation of silymarin proliposome and to compare the pharmacokinetic characteristics and bioavailability after oral administration of silymarin proliposome and silymarin in beagle dogs. Silymarin proliposome was prepared by the film-deposition on carriers. After the proliposome was contacted with water, the silymarin liposome suspensions formed automatically. The tests of physicochemical properties including SEM, TEM, encapsulation efficiency, dissolution studies, particle size of the reconstituted liposome and stability of the silymarin proliposome were determined by laser-particle-sizer, HPLC, etc. The concentrations of silymarin in plasma of beagle dogs and its pharmacokinetic behaviors after oral administration of silymarin liposome suspensions and silymarin were studied by RP-HPLC. The pharmacokinetic parameters were computed by software program 3p97. The encapsulation efficiency of silymarin liposome could be more than 90%, with an average particle size of about 196.4 nm and the proliposome appeared a very stability at 40 degrees C during 3 months. It was found that mean plasma concentration-time curves of silymarin after oral administration of liposome suspensions and silymarin in beagle dogs were both in accordance with open two-compartments model and first-order absorption. Pharmacokinetic parameters of silymarin proliposome and silymarin in beagle dogs were Tmax both 30 min; Cmax 472.62 and 89.78 ng mL(-1); and AUC0-infinity 2606.21 and 697 ng mL(-1)h, respectively. The high bioavailability of silymarin proliposome could be obtained by oral administration. Silymarin proliposome was stable and did enchance the gastrointestinal absorption of silymarin.     

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。     

阿昔洛韦脂质体的制备和稳定性的初步考察阿昔洛韦脂质体的制备和稳定性的初步考察

目的改进阿昔洛韦脂质体的处方和制备工艺，提高脂质体的包封率及稳定性。方法采用逆相蒸发法制备阿昔洛韦脂质体，并在处方中加入表面活性剂，以正交实验优化制备工艺；测定了脂质体包封率和平均粒径；用离心加速实验考察了脂质体的稳定性。结果阿昔洛韦脂质体的平均粒径为219.8 nm，多分散系数为0.158，包封率为65%，具有良好的稳定性。结论实验结果提示该制备工艺和处方可用于制备具有高包封率及稳定性的阿昔洛韦脂质体。     

川陈皮素自组装前体脂质体的制备及其大鼠体内药代动力学研究

本文研制川陈皮素自组装前体脂质体, 并以混悬剂为对照考察其经大鼠灌胃给药后的药代动力学行为。采用一种新型前体脂质体法制备川陈皮素自组装前体脂质体, 考察其水合后粒径、包封率和稳定性等理化性质; 大鼠分别灌胃给予川陈皮素混悬剂和水合后的脂质体, 以尼莫地平为内标, 采用HPLC法测定血浆中药物浓度, 用Kinatica 4.4程序计算药代动力学参数。制得的川陈皮素前体脂质体经水合后包封率可达80%以上,平均粒径为212.1 nm, 稳定性好; 药代动力学研究显示,与混悬剂相比川陈皮素脂质体在体内吸收较快, 相对生物利用度为264.3%, MRT增加。结果表明, 川陈皮素自组装前体脂质体制备工艺简单可行; 川陈皮素制成自组装前体脂质体后, 大鼠口服吸收显著增加。     

Characterization of proliposomes

Photographic evidence of the process of proliposome hydration is provided together with comprehensive particle size analysis of both hydrated dimyristoylphosphatidylcholine: dimyristoylphosphatidylglycerol:ergosterol:amphotericin B proliposomes and egg lecithin:ergosterol:amphotericin B proliposomes using photon correlation spectroscopy and Coulter Counter analysis. Proliposome particle size and the temperature during hydration have been shown to have little effect on subsequent liposome size. A short term stability study of proliposomes indicated that only minor changes in the size distribution profile of the hydrated product are apparent after storage at 20 degrees C for 9 months. Furthermore, no drop in amphotericin B potency was noticed over a 6-month period.     

3种方法制备硫酸卷曲霉素脂质体及其药剂学性质考察

目的:制备硫酸卷曲霉素脂质体并对其性质进行考察。方法:分别采用pH梯度法、硫酸铵梯度法和醋酸钠梯度法3种主动载药法制备硫酸卷曲霉素脂质体并将其制成冻干制剂,通过测定包封率、粒径和ζ电位及考察稳定性等研究脂质体的性质。结果:3种方法制备硫酸卷曲霉素脂质体的包封率冻干前、后分别为65.7%、65.2%,20.1%、18.6%,34.6%、32.4%,粒径分别为136、145nm,144、153nm,142、159nm,ζ电位分别为—20.2、—19.5mV,—24.4、—22.9mV,—18.7、—17.8mV。稳定性考察各项指标均无明显改变。结论:3种方法中pH梯度法更适于制备硫酸卷曲霉素脂质体。     

前列腺素E1脂质体的制备及稳定性初步研究

目的:研制含量稳定、包封率较高的前列腺素E1脂质体制剂,为临床新制剂的开发提供参考.方法:采用逆相蒸发法制备前列腺素E1脂质体,固相萃取-高效液相色谱法测定主药含量及包封率,并用加速试验对制剂的稳定性作出初步考察.结果:前列腺素E1脂质体平均粒径为127.5 nm,包封率为92.35%,具有良好的稳定性.结论:前列腺素E1脂质体制备工艺可行,质量控制方法简单、可靠,该脂质体是一种比较理想的制剂.     

喷雾干燥法制备前体脂质体的基础研究

研究了喷雾干燥法制备前体脂质体（ＰｒｏＬｉｐｏｓｏｍｅ，ＰＬ）的处方工艺，及将ＰＬ水合成重建脂质体（ＲＬ）的可行性，ＲＬ的粒径及影响因素．用丙二醛监测法、碘值法、酸度法考查了脂质体膜材在喷干过程中经受瞬间高温的稳定性．实验结果证明用简单振摇的方法即可将ＰＬ水合为ＲＬ，在通常范围内振摇时间及温度对ＲＬ的粒径无显著影响．制备脂质体所用豆磷脂可以经受喷干的瞬间高温，未有氧化水解等显著破坏，稳定性良好．实验证明，利用制备前体脂质体的方法可以解决脂质体以水溶液形式储存的氧化、水解、聚集、分层等问题，这是脂质体走向工业化生产的关键．与冻干法比，喷干法成本低，生产周期短．喷干法也可适用有机溶媒，这里将更降低喷干的时间和温度，更适于不稳定的药物．此法也可制备无菌制剂．