脂质体佐剂疫苗研究进展

脂质体作为蛋白质及多肽抗原的佐剂和载体已被广泛应用。通过综述脂质体在细菌、病毒、寄生虫和肿瘤疫苗中的研究应用 ,提示脂质体在疫苗的研制中具有广阔的应用前景     

脂质体用作疫苗佐剂的研究进展

脂质体作为疫苗佐剂可同时增强机体的体液和细胞介导免疫应答，对疫苗的增效作用可达数十倍甚至更高。大量动物试验还证实，脂质体也能明显增强抗原性较弱的合成肽和重组抗原的免疫原性，其佐剂疚明显优于铝佐剂，而且毒副反应轻微。脂质体的安全性及高效佐剂作用在部分人体试验中也已得到证实。简便、实用的脂质体制备工艺的建立和完善将进一步加快脂质体佐剂的实用化进程。     

脂质体佐剂疫苗研究进展

脂质体作为蛋白质及多肽抗原的佐剂和载体已被广泛应用。通过综述脂质体在细菌、病毒、寄生虫和肿瘤疫苗中的研究应用，提示脂质体在疫苗的研制中具有广阔的应用前景。     

疫苗佐剂研究进展

在疫苗生产过程中，使用适当的佐剂，不再是单纯地提高机体对抗原的免疫应答水平，而更着重于选择性地诱导产生有效防御相应病原体感染的特异性应答的类型。本文从辅助性Ｔ（Ｔｈ）淋巴细胞亚型及特异性免疫应答类型角度，对新近研究开发的重要选择性佐剂（油性乳剂、脂多糖、皂苷、脂质体以及细胞因子）作一介绍。     

疫苗佐剂的研究进展

新一代疫苗，尤其是重组蛋白或DNA，比传统疫苗反应性弱，免疫原性也小。因此，迫切需要开展和改进疫苗佐剂。根据佐剂的主要作用机制可以将其分为两大类：疫苗输送系统及免疫刺激性佐剂。疫苗输送系统通常为微粒，功能主要是使相关抗原进入抗原提呈细胞。免疫刺激佐剂主要由病原体衍生，模拟病原体相关分子模式，激活先天免疫系统的细胞。更多有效的佐剂的发现促进了对于癌症和慢性感染性疾病的预防和治疗性疫苗的发展。此外，新佐剂的发展也使疫苗经粘膜应用成为可能。     

疫苗用新型非磷脂脂质体的发展现状

磷脂脂质用作疫苗载体与佐剂有许多优点，但因不稳定，原料价高，大规模制备存在困难。，从而限制了它的应用。近年ＭＶＳ公司发明了非磷脂脂质体Ｎｏｖａｓｏｍｅ，稳定性好，价廉，包裹容量高，制备方便，已在疫苗研究及应用中取得进展。本文简述其发展现状。     

疫苗用新型非磷脂脂质体的发展现状

磷脂脂质体用作疫苗载体与佐剂有许多优点,但因不稳定、原料价高,大规模制备存在困难,从而限制了它的应用.近年MVS公司发明了非磷脂质体Novasome,稳定性好、价廉、包裹容量高、制备方便,已在疫苗研究及应用中取得进展.本文简述其发展现状.     

亚单位疫苗佐剂研究进展

接种疫苗是预防、控制甚至消灭传染病最有效的方法。近年来,随着DNA重组技术的发展,重组亚单位疫苗等新型疫苗的研究取得快速发展。亚单位疫苗由病原体的免疫活性片段制备而成,具有制备简单、安全性高等优点,成为新型疫苗的研究开发热点。然而,亚单位疫苗抗原的免疫原性较弱,常需添加佐剂系统增强其免疫作用。因此,本文将对亚单位疫苗中的常用佐剂和新型佐剂研究进展进行综述与分析,旨在为亚单位疫苗的研发提供理论依据。     

新型基因转染阳离子脂质体研究进展

阳离子脂质体是继病毒基因转染载体之后,近几年倍受国内外研究者关注的新一类基因转染载体。本文就用于基因的阳离子脂质体载体的阳离子脂质、载体－ＤＮＡ复合物、载体理化性质及载体肺部基因转染等方面的最新研究进展作一综述。     

阳离子脂质体用作基因转移载的研究进展

鉴于阳离子脂质体制备简便，安全无毒，无免疫原性，近年来在基因转移方面得到了广泛应用。为了列好地适用于体内基因治疗，目前正致力于研制高效，稳定，靶向的阳离子脂质体。     

Water-in-oil solubilized vaccine adjuvants

The solubilization of water and toxoid solutions in oils by non-ionic surface-active agents has been examined. Water-in-oil solubilized adjuvant formulations of vaccines containing Clostridium welchii type D toxoid as antigen have been tested in laboratory animals. The antitoxin titres in rabbit serum induced by the most successful formulation were as high 14 weeks after a single dose, as the peak titres after two doses of a simple aluminium hydroxide adsorbed vaccine. The vaccines are clear and of low viscosity which facilitates accurate measurement and handling by syringe.     

脂质体的研究进展

本文主要介绍了脂质体作为药物靶向制剂载体的研究发展。分析了近年来脂质体在各类药物中的应用及其优点 ,最后提出了目前存在的一些问题及脂质体作为药物载体良好有发展前景     

灯盏花素阳离子脂质体的制备

目的：制备灯盏花素阳离子脂质体和普通脂质体并对其相关性质进行考察。方法：采用薄膜分散法制备灯盏花素脂质体;以包封率为指标,通过正交试验对处方进行优化。考察灯盏花素普通脂质体和阳离子脂质体的体外释放行为。结果：制备的灯盏花素阳离子脂质体性质稳定,包封率为（76.42±1.973）%,平均粒径为（186±35） nm,Zeta电位为（48.9±9.83） mV。灯盏花素普通脂质体和阳离子脂质体的释放过程的拟合方程分别为lnln［1/(1-Q)］=0.779 7lnt-2.318 7(r=0.973 9)和lnln［1/(1-Q)］=0.355 3lnt-3.197(r=0.989 9)。结论：确定了最优处方,制备得到包封率较高且状态稳定的灯盏花素阳离子脂质体。     

Aluminum compounds as vaccine adjuvants

Aluminum compounds are the only adjuvants used widely with routine human vaccines and are the most common adjuvants in veterinary vaccines also. Though there has been a search for alternate adjuvants, aluminum adjuvants will continue to be used for many years due to their good track record of safety, low cost and adjuvanticity with a variety of antigens. For infections that can be prevented by induction of serum antibodies, aluminum adjuvants formulated under optimal conditions are the adjuvants of choice. It is important to select carefully the type of aluminum adjuvant and optimize the conditions of adsorption for every antigen since this process is dependent upon the physico-chemical characteristics of both the antigens and aluminum adjuvants. Adsorption of antigens onto aluminum compounds depends heavily on electrostatic forces between adjuvant and antigen. Two commonly used aluminum adjuvants, aluminum hydroxide and aluminum phosphate have opposite charge at a neutral pH. The mechanism of adjuvanticity of aluminum compounds includes formation of a depot; efficient uptake of aluminum adsorbed antigen particles by antigen presenting cells due their particulate nature and optimal size (<10 μm); and stimulation of immune competent cells of the body through activation of complement, induction of eosinophilia and activation of macrophages. Limitations of aluminum adjuvants include local reactions, augmentation of IgE antibody responses, ineffectiveness for some antigens and inability to augment cell-mediated immune responses, especially cytotoxic T-cell responses.     

Gene delivery using cationic liposomes

The development of cationic liposomes for gene delivery has been ongoing for almost 20 years; however, despite extensive efforts to develop a successful therapeutic agent, there has been limited progress towards generating an effective pharmaceutical product. Since the introduction of N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride, an immense number of different cationic lipids have been synthesised and used to formulate cationic liposome–DNA complexes. Structural modification of the cationic lipids and the addition of components within the delivery system that can facilitate the fusion, cellular uptake and targeting of liposome–DNA complexes have all been used in a bid to enhance their transfection efficiency. Unfortunately, the overall impact of these improvements is still nominal, with the vast majority of clinical trials (～ 85%) continuing to rely on more potent viral delivery of DNA despite their associated toxicity issues. Key characteristics of the most effective cationic liposomes for the delivery of plasmid DNA (from a consensus of the literature) is identified here and the problems of converting these attributes into an effective pharmaceutical product are outlined.     

替尼泊苷长循环阳离子脂质体的制备

目的优化薄膜分散法制备替尼泊苷长循环阳离子脂质体的最佳处方。方法薄膜分散法制备脂质体,以粒径和包封率为考察指标,用单因素考察和正交设计等方法优化脂质体的处方。结果优化后的最佳处方为:磷脂DSPC和PEG 5 000-DOTMA比为4∶1,药物和磷脂比为1∶4,磷脂与胆固醇比为2∶1,乳化剂为卵磷脂。优化的脂质体平均粒径为115.45nm,平均Zeta电位为25.54mV,平均包封率为91.32%,5±3℃放置180d和25±2℃放置30d各项指标变化不显著。结论制备的替尼泊苷长循环阳离子脂质体包封率高,粒径小,释放缓慢,稳定性和安全性好。     

Physicochemical and pharmacokinetic characteristics of cationic liposomes

After intravenous administration of plasmid DNA (pDNA)/cationic liposome complexes, the gene expression is predominantly observed in the lung due to the physicochemical properties of the liposome complexes and the physiology of the lung. To determine the physicochemical properties and distribution behavior of cationic liposomes for lung-selective drug and/or gene delivery systems, N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride (DOTMA)/cholesterol and 1,2-dioleoyl-3-trimethyl-ammoniopropane (DOTAP)/cholesterol liposomes were studied. The particle sizes of DOTMA/cholesterol and DOTAP/cholesterol liposomes were very similar: 126 and 128 nm, respectively. Furthermore, the zeta potentials of these two liposomes were 51 and 66 mV, respectively. After intravenous injection into mice, both cationic liposomes were rapidly eliminated from the blood circulation and preferentially recovered in the lung. Interestingly, the highest lung accumulation was observed at 1 min, and then, decreased gradually. The distribution characteristics of DOTMA/cholesterol and DOTAP/cholesterol liposomes were almost identical due to the similarities in their physicochemical properties. These results demonstrated that DOTMA/cholesterol and DOTAP/cholesterol liposomes, which possess a positive charge, are promising carriers for lung-selective drug and/or gene delivery systems.     

Vascular targeting of doxorubicin using cationic liposomes

Tumor vessel has been recognized as an important target for anticancer therapy. Cationic liposomes have been shown to selectively target tumor endothelial cells, thus can potentially be used as a carrier for chemotherapy agents. In this study, cationic liposomes containing 20 mol% cationic lipid dimethyl dioctadecyl ammonium bromide (DDAB) and loaded with doxorubicin (DOX) were prepared and characterized. The cationic liposomal DOX showed 10.8 and 9.1 times greater cytotoxicity than control PEGylated liposomal DOX in KB oral carcinoma and L1210 murine lymphocytic leukemia cells, and 7.7- and 6.8-fold greater cytotoxicity compared to control neutral non-PEGylated liposomal DOX, repectively, in these two cell lines. Although cationic liposomal DOX had higher tumor accumulation at 30 min after intravenous administration compared to control liposomes (p<0.05), DOX uptake of these liposomes at 24h post-injection was similar to that of PEGylated liposomal DOX (p>0.05) and approximately twice the levels of the free drug and non-PEGylated liposomes. In a murine tumor model generated using L1210 cells, increased survival rate was obtained with cationic liposomal DOX treatment compared to free DOX (p<0.01), neutral liposome control (p<0.01), as well as PEGylated liposomes (p<0.05). In conclusion, the cationic liposomal DOX formulation produced superior in vitro cytotoxicity and in vivo antitumor activity, and warrants further investigation.     

阳性脂质体介导基因转染及其研究进展*

基因治疗是一种很有前景的治疗模式,而阳性脂质体介导的基因转染是目前基因治疗的研究热点之一。现综述近5年来有关阳性脂质体的文献,介绍了阳性脂质体的基本组成,并从生物学、理化性质及制剂学等几个方面介绍了影响阳性脂质体/DNA复合物转染效率的主要因素,最后从新的阳性脂质成分及阳性脂质体或阳性脂质体/DNA复合物的表面修饰等方面介绍了近年来有关改善阳性脂质体介导基因转染的研究进展。