粉尘螨脂质体的制备及稳定性考察

目的研究冻融法对粉尘螨(Dermatophagoides farinae,DF)脂质体包封率、形态及稳定性影响。方法采用逆向蒸发法制备粉尘螨脂质体悬液,冰冻高速离心法分离脂质体,透射电镜观察脂质体形态。-20℃低温冰箱冰冻,室温融化,反复5次,测定冻融前后脂质体包封率及形态变化,并用离心加速实验测定脂质体稳定性变化。结果经冻融法处理的脂质体包封率明显提高,可达(88.52±0.87)%;在一定范围内包封率随冻融次数的增加而略有增大;经离心加速实验进一步验证了冻融法可使脂质体稳定性提高。结论冻融法为一有效的脂质体制备方法。     

冻融法制备5-氟尿嘧啶脂质体及其稳定性考察

采用反相蒸发法制备 5 氟尿嘧啶脂质体制剂 .结合冻融法 ,可使 5 氟尿嘧啶的包封率达(45 31± 0 2 0 85 ) % .离心加速实验和 ζ电位的测定进一步验证了冻融法可使脂质体稳定性提高 .     

酸敏脂质体的制备及其生物学活性

目的　对不同方法制备酸敏脂质体进行包封率测定及形态学观察 ,探讨酸敏脂质体包裹反义寡核苷酸的生物学效应。方法　测定四种不同方法制备包裹1 2 5I IL 8脂质体的包封率 ;在超高倍显微分析仪下观察形态结构。用包裹细胞磷脂酶A2 (cPLA2 )反义寡核苷酸的酸敏脂质体转染U937细胞 ,提取细胞RNA ,采用反转录 聚合酶链反应 (RT PCR) ;免疫印迹 (Westernblot)法检测cPLA2 蛋白的表达。结果　反相蒸发法与钙融合法联合制备的酸敏脂质体具有良好地包封率和形态结构 ,经酸敏脂质体包裹cPLA2 反义寡脱氧核苷酸可明显抑制cPLA2基因及蛋白的表达。结论　制备所得的酸敏脂质体可良好的发挥其生物学效应     

黄芩苷脂质体的制备和稳定性考察

目的:改进黄芩苷脂质体的制备工艺,提高脂质体的包封率及稳定性.方法:采用逆相蒸发法、乙醚注入法和薄膜超声法制备黄芩苷脂质体;测定脂质体包封率和平均粒径;用离心加速实验考察脂质体的稳定性.结果:5批黄芩苷脂质体的平均粒径为(360±42)nm,包封率为(56.0±5.3)%.结论:实验结果提示逆相蒸发法可用于制备具有较高包封率及稳定性的黄芩苷脂质体.     

逆相蒸发法制备多层脂质体:结构和最佳包裹量

逆相蒸发法(REV)是制备单层脂质体的方法,有较高的包裹率。近年来,改良的REV可获得两种多层脂质体:MLV-REV脂粒和SPLV脂粒。MLV-REV脂粒的包裹率近65%,SPLV脂粒的包裹率为35～40%。本文的目的是进一步提高MLV-REV法的包裹率,并探讨其脂粒结构特征,与SPLV法制成的多层脂粒进行比较。 Small等曾比较平面双分子层包裹的水容积和脂质体包裹的水容积,以此来阐明脂质体的结构。作者用X-线衍射测量,表明MLV-REV和SPLV脂粒中的长空间(long spacing)与平面双分子层的长空间相似。因     

脂质体鬼臼毒素混悬液的制备及包封率测定

目的:制备脂质体鬼臼毒素混悬液,观察脂质体鬼臼毒素在电镜下的形态及粒径范围,观察脂质体鬼臼毒素混悬液的稳定性,测定混悬液中脂质体鬼臼毒素的包封率,并观察脂质体鬼臼毒素包封率的稳定性.方法:采用逆向薄膜蒸发法制备脂质体鬼臼毒素混悬液,观察透射电镜下脂质体鬼臼毒素的形态,混悬液低温离心后采用紫外分光光度法测定脂质体鬼臼毒素的包封率.结果:制备的脂质体鬼臼毒素混悬液稳定性较理想,脂质体包封率为71.1%,1,3,6个月的脂质体包封率分别为:70.9%,60.8%,54.9%.结论:制备的脂质体鬼臼毒素混悬液稳定性较理想,脂质体包封率较高,但包封率的稳定性有待进一步提高.     

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。     

靶向给药系统——青蒿酯脂质体的制备研究

采用乳化法制备了多层的青蒿酯脂质体,探讨了其制备工艺、荷电性、胆固醇含量及附加剂对青蒿酯脂质体包裹率的影响。结果表明,带正电荷的脂质体其包裹率明显高于中性或带负电荷的脂质体,而类脂中胆固醇含量及附加剂对包裹率均无明显影响,最佳处方组成的包裹率为3.63±0.09％。采用冷冻干燥技术可获得稳定性较好的脂质体冻     

新疆紫草提取物脂质体制备工艺的初步筛选

目的:筛选新疆紫草提取物脂质体的制备工艺。方法:分别采用薄膜分散法、逆相蒸发法、乙醇注入法、乙醚注入法和熔融法制备新疆紫草提取物(AEE)脂质体,以包封率、形态、粒径分布等为指标比较5种方法的适用性。结果:薄膜分散法、逆相蒸发法、乙醇注入法与乙醚注入法制得的脂质体形态较完整,大小较均匀;其中乙醇注入法制备的AEE脂质体包封率最高,为(63.53±0.71)%。结论:乙醇注入法适合于AEE脂质体的制备。     

卵磷脂质量对甲氨喋呤(MTX)脂质体包裹率的影响

本文研究了卵磷脂的理化性质与MTX脂质体包裹率的关系。分别测定了两种卵磷脂(大豆卵磷脂、蛋黄卵磷脂)的氧化指数、碘价、紫外吸收光谱及薄层层析,并用具有不同氧化指数的卵磷脂用二次乳化蒸发法制备MTX脂质体,测定它们包裹MTX的百分率。初步表明:卵磷脂对药物包裹率随其氧化指数的升高而降低,同时薄层层析的杂质点亦增多。实验结果提示,用氧化指数在0.2以下,碘价在60左右,以及薄层层析一个点的卵磷脂制备MTX脂质体可以得到较高的包裹率。     

Differential Disposition of Soluble and Liposome-Formulated Human Recombinant Interleukin-7: Effects on Blood Lymphocyte Population in Guinea Pigs

The effects of liposome formulation on interleukin-7 (IL-T)-dependent lymphopoietic activity was investigated based on the pharmacokinetics and tissue distribution profile of soluble and liposome-formulated recombinant human IL-7. Using ¹²⁵I-IL-7, we determined the role of liposome formulation on in vivoIL-7 disposition by analyzing injection site, blood, tissue, and urinary kinetics. Following a 30- to 40-µg subcutaneous dose of soluble IL-7, most of the IL-7 was eliminated through urinary excretion within 24 hr. An equivalent subcutaneous dose of liposome-encapsulated IL-7 resulted in a peak level less than one-tenth that seen with soluble drug but produced sustained blood and urinary levels for 5 days. The bioavailability of liposome-encapsulated IL-7 was comparable to that of soluble IL-7, as determined by both blood and urinary data. Kinetic analysis of IL-7 at the subcutaneous injection site indicated that liposome encapsulation significantly reduced the rate of disappearance at the injection site. Studies with a mixture of 40% liposome-encapsulated and 60% soluble IL-7 gave an intermediate response between that of soluble IL-7 and that of liposome-encapsulated IL-7. Characterization of blood cells from IL-7-treated animals indicated that treatment with two weekly doses of mixed IL-7 liposomes (40% liposome encapsulated IL-7) significantly increased the total numbers of lymphocytes by day 14. In contrast, animals treated with soluble IL-7 on an identical dose and schedule did not produce any effect on blood lymphocytes. Collectively, liposome formulation provided a lower, but significantly sustained blood IL-7 level that enhanced IL-7 effects on blood lymphocyte numbers.     

阿糖腺苷毫微囊的化学稳定性研究

本文应用反相HPLC建立了阿糖腺苷毫微囊(Ara-A-NC)混悬型注射剂中Ara-A的含量测定方法,并以此法研究了Ara-A-NC的化学稳定性。结果表明,Ara-A-NC注射剂中Ara-A受热作用,按一级动力学降解,降解反应的活化能为46.49kJ/mol,初步预测Ara-A-NC有效期为10.47个月(25℃).     

丹参酮脂质体的制备及其稳定性

采用冻融法制备了丹参酮的脂质体,比较了冻融前后丹参酮脂质体的包封率,粒度分布,形态以及稳定性,并考察了冻融次数及冻融之后的搅拌和超声对脂质体的包封率和粒度分布的影响。结果表明,经冻融处理的丹参酮脂质体的包封率明显提高,稳定性也更好;一定范围内,脂质体的包封率和粒度随冻融次数的增加而略有增大,冻融后搅拌或超声均可使聚集的脂质体解聚,从不影响包封率的角度,搅拌比超声处理更好。     

阿糖腺苷毫微囊的药代动力学研究

建立了反相HPLC测定血浆中阿糖腺苷的方法。研究和比较了阿糖腺苷溶液型注射剂和毫微囊型注射剂在家兔体内的药代动力学。毫微囊使阿糖腺苷在体液中维持较高的浓度和较长的时间。     

In vitro and in vivo characterizations of PEGylated liposomal doxorubicin

One challenge in developing a nanoparticle drug-delivery system is understanding the critical physicochemical properties that may impact its in vivo performance and establishing analytical techniques that can adequately characterize in vitro and in vivo properties. Doxil?/Caelyx?, a PEGylated liposomal doxorubincin (PLD), is one of the leading approved nanoparticle product used in cancer therapy. In this review, we use PLD as an example to illustrate identification of key in vitro and in vivo characteristics. The following characteristics, including liposome composition, state of encapsulated drug, internal environment of liposome, liposome size distribution, lamellarity, grafted polyethylene glycol at the liposome surface, electrical surface potential or charge, and in vitro leakage, are considered critical to demonstrate the supramolecular structure of PLD and ensure consistent drug delivery to cancer tissues. Corresponding analytical techniques are discussed to determine these liposome characteristics. Furthermore, in vivo stability of the PLD can be determined by plasma pharmacokinetics of both free and liposome-encapsulated drug. A better understanding of the critical in vitro and in vivo liposome characteristics together with improvements in analytical technology will enable generic liposome product development and ensure liposome product quality.     

阿昔洛韦脂质体的制备与稳定性实验的考察

目的利用薄膜分散法将阿昔洛韦制成脂质体改变口服生物利用度低的缺点。方法采用高效液相色谱法测定包封率并对其稳定性进行考察。结果在2～20.0μg·mL-1范围内,呈现良好线性关系(r=0.9999),包封率稳定。结论HPLC能够满足分析的需要,包封率达到90%以上。     

Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery system

Liposome-encapsulated drugs often exhibit reduced toxicity and have also been shown to enhance retention of drugs in the tissues. Thus, encapsulation of drugs in liposomes has often resulted in an improved overall therapeutic efficacy. The results of efficacy of liposome-encapsulated ciplofloxacin or azithromycin for therapy of intracellular M. avium infection show enhanced cellular delivery of liposome-encapsulated antibiotics and suggest that efficiency of intracellular targeting is sufficient to mediate enhanced antimycobacterial effects. The antitubercular drugs encapsulated in lung specific stealth liposomes have enhanced efficacies against tuberculosis infection in mice. These results from stealth liposome study indicate that antitubercular drugs encapsulated in liposome may provide therapeutic advantages over the existing chemotherapeutic regimen for tuberculosis. Liposomes with encapsulated amikacin are able to protect collagen almost completely from adherence of bacterial cells of all strains examined and prevent from invading of bacteria.     

Brain, liver and spleen detection of liposomes after rectal administration

Bangham-type liposomes, undergoing freeze-thawing cycles, were detected electron microscopically in the brain, liver and spleen of experimental animals 24 h after rectal administration. This novel approach has several important advantages over intravenous, intraperitoneal and other usual means of administration of liposome drug-entrapped treatment and diagnostics for human application. The location of the liposomes in the brain after rectal administration shows that the brain-blood barrier can be overcome successfully by this method. Moreover, the risk of embolism and hypersensitivity, strict control of sterility and some other undesirable effects can be avoided. The possible role of rectal administration in the development of liposome drug-entrapped treatment and diagnostics is discussed.     

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.     

Preparation and evaluation of semi-permanent hair dyes liposome

This study used phospholipids from fresh egg yolks to prepare liposome-encapsulated semi-permanent hair dyes in different pH buffer solutions and evaluated the functions and colour fastness to washing of the dyes. The extraction ratio of egg yolk phospholipids was 5%, and the purity was 91.8%. Empty liposome solutions were then prepared using high-speed homogenizer with particle size 219-848?nm. After being stored at 4 °C for 28 days, the average particle size of the liposome-encapsulated dye formulas increased from 1.36-1.92?μm to 1.99-2.38?μm. The ΔE colour difference values of the five hair extension sets dyed with the control group and hair dyes on the market were of the range 6.56-13.39 after eight times of washing, whereas the ΔE values of the four hair extension sets dyed with the liposome-encapsulated dyes were of the range 3.56-5.21 after eight times of washing. The liposome-encapsulated dye at pH 3 showed the best result.