新型强化材料修饰脂质体的研究进展

综述强化材料修饰的脂质体的研究现状和发展趋势。围绕目前正在进行临床试验研究阶段的脂质体制剂,如多糖修饰脂质体、甘草次酸修饰脂质体、聚乙二醇修饰脂质体、PAC膜修饰脂质体、RGD修饰脂质体、聚赖氨酸修饰脂质体、泊洛沙姆修饰脂质体等,分析用强化材料修饰后的脂质体在稳定性、靶向性、体内循环作用时间等方面的提高情况,并对脂质体存在的问题及设计中应该注意的方面和今后发展可行性进行了探讨。     

主动靶向脂质体在抗肿瘤治疗中的研究进展

主动靶向脂质体给药系统可使抗肿瘤药物与靶组织结合,将药物可控性地分布于靶组织并持续缓慢释药,在提高药物抗癌效果的同时,降低了其对正常组织的不良反应。本文主要介绍了免疫脂质体、受体介导的脂质体、糖基修饰的脂质体及多肽修饰的脂质体等主动靶向脂质体在抗肿瘤研究中的进展。主动靶向脂质体给药系统将会发展为抗肿瘤药物的理想剂型,具有很好的临床应用前景。     

甘草次酸修饰多西紫杉醇脂质体的制备和体外抑瘤效果

目的:制备甘草次酸(GA)修饰的多西紫杉醇脂质体,并初步考察其体外抗肿瘤效果.方法:化学合成甘珀酸十八醇酯(18-GA-Suc)作为修饰材料,采用薄膜分散法制备甘草次酸修饰的多西紫杉醇脂质体,考察影响脂质体包封率的因素.采用MTT法评价脂质体对HepG2细胞的体外抑瘤效果.结果:18-GA-Suc修饰的DX脂质体的体外抑瘤效果强于未修饰的DX脂质体,并且抑瘤效果随着载体中18-GA-Suc的增加而增强.结论:甘草次酸修饰的脂质体有望成为新型肝靶向的抗肿瘤载体.     

应用强化材料修饰脂质体提高肝靶向性

介绍强化材料修饰脂质体以提高肝靶向性的应用及发展状况.围绕目前正在进行临床研究阶段的脂质体制剂,分析其用强化材料修饰脂质体后肝靶向性提高方面的情况.     

PEG修饰水飞蓟素脂质体的制备及体外释放研究

目的:合成一种PEG硬脂酸单酯,应用Box-Behnken设计优化PEG修饰水飞蓟素脂质体的处方和工艺.方法:采用IR、1H-NMR法表征PEG硬脂酸单酯的结构,采用改进的薄膜分散法制备修饰脂质体,血浆透析法比较脂质体与修饰脂质体的体外释放曲线.结果:水飞蓟素修饰脂质体最佳处方含大豆磷脂:胆固醇:PEG硬脂酸单酯:水飞蓟素为20:4.8:0.9:1(w/w),修饰脂质体的平均粒径为100.9nm,包封率为91.2%,体外释放动力学符合Weibull方程.结论:PEG修饰水飞蓟素脂质体体外释放缓慢,注射给药体内能达到长循环作用.     

用于抗肿瘤药物递送的脂质体表面修饰策略

脂质体作为一种传统的药物传递系统,因其在药物及蛋白质、基因、核酸等生物活性物质的高效传递方面的应用而备受研究领域的关注。脂质体给药系统在抗肿瘤药物研究领域经历了常规脂质体、长循环脂质体、配体功能脂质体、刺激响应型脂质体等4个阶段。现结合相关文献,综述了这4种脂质体给药系统常用的表面修饰靶向策略和研究进展,以期为脂质体的进一步研究和基本靶向修饰提供参考。     

脂质体表面修饰的研究新进展

脂质体具有一定靶向性,而修饰后的脂质体具有主动靶向性、抗癌性更强,是目前研究较多的一种新技术,笔者就现在几种比较常见的修饰脂质体进行简单介绍。     

配体修饰脂质体的研究进展

目的:寻找较为稳定、有效且制备方法可靠的新的配体修饰脂质体(Ligand-modified liposomes,LML)。方法:查阅配体修饰脂质体的相关文献,综述了叶酸、甘露糖基、抗体、肽等不同配体修饰的脂质体的研究进展。结果与结论:配体修饰后的脂质体在靶向性与药效学方面有明显的提升,但也面临着巨大的挑战,如抗体和蛋白质等大分子配体会增加脂质体的免疫性,加快脂质体的循环清除等。配体修饰脂质体作为药物载体将会逐渐在疫苗接种、基因转染、靶向制剂方面发挥更加重要的作用。     

提高脂质体主动靶向性材料的研究进展

目的:为制备高效的脂质体提供参考。方法:以"材料""脂质体""Materials modified liposomes"等为关键词,组合查询2000-2016年在Pub Med、中国知网、万方、维普等数据库中的相关文献,对修饰脂质体材料的种类、特点及其在制剂中的应用研究进行综述。结果与结论:共检索到相关文献439篇,其中有效文献45篇。目前用于修饰脂质体的材料主要有糖类及其衍生物、配体类、聚合物类及肽类等。其中糖类及其衍生物、配体类和肽类修饰后的脂质体具有主动靶向性,能提高药物的生物利用度;聚合物类修饰后的脂质体可提高药物的稳定性。目前国内修饰脂质体材料还处在研发阶段,临床应用较少,存在经修饰的脂质体在体内外的靶向性是否具有可比性、各类材料是否能广泛用于不同含药脂质体的修饰、修饰后的脂质体能否实现大规模生产、修饰脂质体的设计与制备过程均较普通脂质体复杂等问题,有待今后去攻克。     

抗体介导的免疫脂质体的研究进展

免疫脂质体作为靶向药物传递体系,以其增效减毒的特性在肿瘤诊断及治疗等领域具有独特的优势,相关研究也得到越来越多的重视.目前,免疫脂质体的制备工艺逐渐完善,选择合适的偶联方案对制剂的活性及稳定性至关重要.了解靶向分子结构及偶联反应机理有助于更好地选择修饰和连接技术,有效实现免疫脂质体靶向传递的作用.本文就免疫脂质体中抗体的类型、抗体和磷脂的修饰技术以及抗体偶联脂质体的方法进行综述.     

Antibody-targeted liposomes in cancer therapy and imaging

Background: Targeted liposomes can be broadly defined as liposomes that are engineered to interact with a particular population of cells with the objective of delivering a payload or increasing their retention within the targeted cell population by means of a chemical interaction with cell-surface molecules or other tissue-specific ligands. Objective: The authors review recent advances in the field with an emphasis on pre-clinical studies and place them in the context of historical developments. Methods: The review focuses on immunoliposomes (antibody-mediated targeting) as these constructs are presently the most prevalent. Conclusion: The field has advanced in tandem with advances in liposome design and antibody and protein engineering. Targeted liposomes have been used in diagnosis to deliver magnetic resonance contrast agents and radionuclides for magnetic resonance and nuclear medicine imaging, respectively. They have been used in gene therapy to deliver a variety of gene expression modifiers, including plasmids, anti-sense oligonucleotides and short interfering RNA. Targeted liposomes provide a delivery advantage over untargeted liposomes not because of increased localization to tumor sites but because of increased interaction with the target cell population once localized to the tumor site. The increased interaction can take on the form of fusion with the cellular membrane or internalization by endocytosis. To the extent that the spatial distribution of targeted liposomes within a solid tumor may become more non-uniform than has been found for untargeted liposomes, this may be a drawback. However, systematic comparisons of the spatial distribution in tumors of targeted versus untargeted liposomes have yet to be performed. The majority of reported studies have been in the area of chemotherapy delivery. Their use in radionuclide and chemo- and radiosensitizer delivery is just emerging. Multifunctional liposomes containing ‘layered functionalities’ could potentially be the future direction in targeted liposome-based therapy.     

长循环脂质体在抗肿瘤药物中的应用进展

长循环脂质体可改善抗肿瘤药物的不良反应,增加靶向性,延长血循环时间,增强抗癌疗效。综述长循环脂质体在各种抗肿瘤药物中的应用和新型长循环脂质体的概况,并对长循环脂质体治疗肿瘤的前景进行展望。     

新型热敏脂质体的研究进展

综述了近几年出现的新型热敏脂质体：长循环热敏脂质体，磁性热敏脂质体，免疫热敏脂质体和多聚物热敏脂质体     

Nasal Delivery. The Use of Animal Models to Predict Performance in Man

Abstract

Galactose and Mannose residues were tagged on the surface of n-glutaryl-phosphatidyl-ethanolamine (NGPE) containing liposomes with and without polyethylene glycol of molecular weight 2000 Da conjugated to distearoyl phosphatidylethanolamine (PEG-2000-DSPE). Biodistribution studies showed that sugar bearing liposomes were cleared more rapidly from circulation than those not bearing the sugar moieties. However, the rate of clearance of glycosylated conventional liposomes was much faster than the sugar bearing sterically stabilized liposomes. Intrahepatic distribution studies showed that a substantial amount of conventional liposomes without sugar residues were taken up by both parenchymal (P) (40%) and non-parenchymal (NP) cells (60%). However, incorporation of PEG-2000-DSPE shifted this uptake slightly in favour of parenchymal cells (47%). While ratio of distribution of galactosylated conventional liposomes to P and NP cells was found to be 74: 26, galactosylation of sterically stabilized liposomes further enhanced the affinity of these vesicles towards P cells (P: NP ratio being 93: 7). Thus, reduced uptake by Kupffer cells was observed with galactosylated sterically stabilized liposomes as compared to conventional liposomes. Whereas, mannosylation of both the liposomes shifted the distribution towards Kupffer cells in an analogous manner. These findings indicate that sterically stabilized liposomes tagged with galactose residues on their surface are more effective in targeting the entrapped material to hepatocytes as compared to conventional liposomes. This approach can therefore be employed for delivering therapeutic agents like drugs, enzymes, genetic materials, anti-sense oligonucleotides selectively to liver P cells for treatment of hepatic disorders.     

Acacia-Gelatin Microencapsulated Liposomes: Preparation,Stability, and Release of Acetylsalicylic Acid

Liposomes of dipalmitoylphosphatidylcholine (DPPC) containing acetylsalicylic acid (ASA) have been microencapsulated by acacia-gelatin using the complex coacervation technique as a potential oral drug delivery system. The encapsulation efficiency of ASA was unaltered by the microencapsulation process. The stability of the microencapsulated liposomes in sodium cholate solutions at pH 5.6 was much greater than the corresponding liposomes. The optimum composition and conditions for stability and ASA release were 3.0% acacia-gelatin and a 1- to 2-hr formaldehyde hardening time. Approximately 25% ASA was released in the first 6 hr from microencapsulated liposomes at 23°C and the kinetics followed matrix-controlled release (Q t ^l/2). At 37°C, this increased to 75% released in 30 min followed by a slow constant release, likely due to lowering of the phase transition temperature of DPPC by the acacia-gelatin to near 37°C. At both temperatures, the release from control liposomes was even more rapid. Hardening times of 4 hr and an acacia-gelatin concentration of 5% resulted in a lower stability of liposomes and a faster release of ASA. It is concluded that under appropriate conditions the microencapsulation of liposomes by acacia-gelatin may increase their potential as an oral drug delivery system.     

脂质体修饰性材料应用研究进展

脂质体作为低毒性与免疫原性的药物载体已被应用于难溶性、不稳定、毒性等药物的递送，但传统脂质体仍存在稳定性差、体内循环时间不足、主动靶向性不明显等缺陷，因此选择适宜的修饰性材料制备脂质体已成为必要手段。修饰脂质体的方法主要有：在膜材中加入表面活性剂或改性物质，在膜表面嵌插靶向配体物质，将配体与膜材偶联共同组成脂质体结构。通过总结近年来脂质体常用的修饰性材料，阐释修饰原理并分析其优势及弊端，为脂质体的研究与开发提供借鉴。     

脂质体物理化学稳定性研究进展

目的了解影响脂质体稳定性的作用机制,从根本上控制脂质体的稳定性。方法综述了物理、化学两个方面影响脂质体稳定性的因素。结果与结论以脂质体的粒径、渗漏率、载药量等为指标评价其稳定性,并通过改变脂质体组成、改进制备方式、制备新型脂质体等方法提高脂质体的稳定性。     

醋酸亮丙瑞林脂质体及壳聚糖包衣脂质体经肠道及Caco-2细胞转运机制

目的考察醋酸亮丙瑞林脂质体及壳聚糖包衣脂质体经大鼠肠道及Caco-2细胞的转运机制。方法应用翻转肠囊法和Caco-2 细胞模型考察游离醋酸亮丙瑞林、脂质体包封的醋酸亮丙瑞林以及壳聚糖包衣脂质体中醋酸亮丙瑞林的转运特征。在Caco-2细胞水平考察壳聚糖浓度、加入次序对脂质体中醋酸亮丙瑞林渗透的影响。结果游离醋酸亮丙瑞林的转运符合被动扩散的性质。相同实验条件下，脂质体中药物渗透量低于游离药物。可能是由于脂质体包封醋酸亮丙瑞林，阻止了药物向肠囊和Caco-2细胞转运。但是脂质体对酶降解醋酸亮丙瑞林具有保护作用。壳聚糖促进脂质体中亮丙瑞林的转运，壳聚糖的促渗作用在0.1%-0.5%浓度范围无明显差异。壳聚糖包覆脂质体后的促渗作用弱于其单独使用的促渗作用。结论壳聚糖包衣醋酸亮丙瑞林脂质体兼有保护和促渗作用，可能促进醋酸亮丙瑞林的口服吸收。     

Safety,efficacy and pharmacokinetics of tuftsin-loaded nystatin liposomes in murine model

Present study was performed to evaluate the efficacy, toxicity and pharmacokinetics of antifungal drug nystatin incorporated in immunomodulator tuftsin-bearing liposomes. In vitro toxicity of free nystatin and nystatin incorporated in tuftsin-free or tuftsin-loaded liposomes was assessed by incubation of nystatin formulations with human erythrocytes. The toxicity profile of free nystatin and liposomal formulations of nystatin with or without tuftsin was also analyzed by monitoring the level of blood urea nitrogen (BUN) and serum creatinine in the treated BALB/c mice. The results of the present work showed that tuftsin-loaded nystatin liposomes like conventional nystatin liposomes exerted less toxicity to human erythrocytes as compared with free nystatin. Moreover, mice treated with tuftsin-loaded nystatin liposomes showed insignificant elevation in the biochemical values of serum creatinine and blood urea. The stability of nystatin liposomes upon incorporation of tuftsin was evaluated by monitoring the leakage of the entrapped drug in human serum. Tuftsin-loaded liposomes held nystatin for longer duration in the presence of serum than identical nystatin liposomes without tuftsin. Pharmacokinetics of the both tuftsin-free or tuftsin-loaded liposomal formulations nystatin was analyzed by determining the level of nystatin in the systemic circulation of mice at different time points. Mice injected with tuftsin-loaded nystatin liposomes showed higher level of the drug in the systemic circulation compared with those treated with conventional nystatin liposomes. The efficacy of tuftsin-loaded nystatin liposomes against A. fumigatus was evaluated by assessing the fungal burden in the lungs of treated mice. Treatment with tuftsin-loaded nystatin liposomes was most effective in eliminating fungal burden from lung tissues of infected mice compared to those treated with free nystatin or nystatin liposomes without tuftsin. The immunopotentiating activity, increased stability and less toxicity of tuftsin-incorporated nystatin liposomes, supports the idea for its prophylactic and therapeutic use in the clinical setting.