聚乙二醇修饰的立体稳定脂质体

立体稳定脂质体（长效脂质体）是一种表面含有天然或合成聚合物修饰的类脂衍生物的新型脂质体。它在血液中驻留时间延长，从而延长药物作用时间，具有长效作用。将抗体或其他配体连接于长效脂质体表面的聚合物末端，可得到立体稳定的免疫脂质体，从而达到长效与靶向的完善结合。     

聚乙二醇POPA磷脂衍生物构建的酶敏脂质体

以磷酰胺键将聚乙二醇高分子MePEG2000-NH₂与磷脂POPA连接在一起, 合成聚乙二醇磷脂衍生物, 以聚乙二醇磷脂衍生物为主要膜材构建酸敏脂质体。采用荧光分析法系统研究了聚乙二醇磷脂衍生物脂质体在酸性条件下对荧光染料的释药特性。以聚乙二醇磷脂衍生物构建的酸敏脂质体,在pH 6.5～7.5时稳定,其稳定性与制备脂质体的磷脂种类及胆固醇含量密切相关,在pH 5.0时发生显著的荧光泄漏,泄漏率与环境酸性的强度及处于酸性的时间呈正相关。聚乙二醇磷脂衍生物构建的脂质体具有开发成酸敏释药脂质体的前景。
     

聚乙二醇化尿酸酶脂质体的稳定性研究

目的 制备聚乙二醇化尿酸酶脂质体(PULPs)并考察其活性与稳定性.方法 采用逆向蒸发法制备PULPs,并考察其最适温度、最适pH、热稳定性、贮存稳定性及其抗胰蛋白酶水解的能力、抗部分金属离子及有机化合物影响的能力.结果 PULPs的最适温度为40℃,最适pH为8.5;PULPs的热稳定性、贮存稳定性、抗胰蛋白酶水解能力、抗部分金属离子及有机化合物影响的能力均优于尿酸酶.结论 PULPs在增强聚乙二醇化尿酸酶活性的同时增强了稳定性.     

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。     

聚乙二醇-脂质衍生物修饰对脂质体稳定性的影响

聚乙二醇-脂质(polyethylene glycol-lipid,PEG-lipid)衍生物具有增加脂质体的稳定性、延长其血液循环半衰期、提高其肿瘤靶向效率及增强药物疗效等优势。深入研究不同PEG-lipid衍生物修饰对脂质体的物理、化学和生物学稳定性的影响,有利于解决目前PEG化脂质体存在的问题,如静脉重复注射时引起的加速血液消除(accelerated blood clearance,ABC)现象,为开发新型靶向制剂奠定基础。本文主要综述了PEG与脂质之间的连接键如酰胺键、醚键、酯键和二硫键,脂质种类如常用的磷脂酰乙醇胺、胆固醇和二酰甘油,脂质的性质即脂肪链长度与饱和度,PEG的端基如甲氧基、羧基、氨基,PEG的相对分子质量和PEG-lipid的摩尔比对PEG化脂质体在体内外稳定性的影响。     

提高脂质体稳定性研究进展

脂质体是人工制备的由磷脂双分子定向排列而成的微球。脂质体自20世纪70年代开始作为药物载体应用以来 ,由于具有制备简单 ,对人体无害 ,无免疫原性反应 ,易实现靶向性 ,可提高和延长药物疗效 ,缓和毒性 ,避免耐药性和改变给药途径等优点备受重视。但脂质体的应用范围受到其稳定性的限制。脂质体在储存过程中 ,由于药物渗漏、粒子的聚集以及磷脂在液态下的氧化水解等原因易被破坏 ;进入体内后 ,由于血中的白蛋白、调理素、抗体等各种物质的作用 ,脂质体可能发生破裂 ,致使包封药物快速渗漏 ,很快被网状内皮系统识别、吸收 ,从体循环中清除 ,…     

聚乙二醇在脂质体中的作用

兼有亲水性和柔顺性的聚乙二醇高分子,能在脂质体表面形成一层水化膜,阻碍血浆成分与脂质体表面的吸附,从而降低网状内皮系统对脂质体的摄取,使脂质体在体循环中的时间延长。本文从作用机理角度,综述聚乙二醇对脂质体及免疫脂质体的稳定性和药物动力学的影响,以及其在脂质体中的应用。     

不同类型的磷脂对三氧化二砷脂质体外观稳定性的影响

目的:研究不同类型的磷脂对三氧化二砷(As2O3)脂质体外观稳定性的影响。方法:采用A、B厂家生产的浓缩磷脂和C、D厂家生产的粉状磷脂,分别应用薄膜分散法、乙醚注入法、逆相蒸发法制备脂质体,以样品是否发生分层凝聚现象为指标观察其在1、7d,1、6、12个月内的外观稳定性。结果:A、B2厂家磷脂制备的As2O3脂质体在1年内全部出现分层凝聚现象,C、D厂家磷脂制备的As2O3脂质体保存1年仍未见分层凝聚现象。结论:C、D2个厂家所生产的磷脂制备的As2O3脂质体稳定性更好,不同类型的磷脂对所制备的脂质体的外观稳定性具有一定影响。     

载药脂质体物理化学稳定性的研究进展

脂质体是一种新型药物载体，研制出稳定的脂质体是脂质体作为药物载体走向实用的前提，具有十分重要的意义。本文综述了影响脂质体物理、化学稳定性的主要因素及部分作用机制；并对改进脂质体稳定性的方法，从加入抗氧化物质、应用冰冻干燥和选择合适的磷脂种类等几个方面进行了阐述。结果表明，单纯的将脂质体的稳定性分为化学和物理稳定性是不够的，弄清楚影响脂质体稳定性的机制，找到确切的影响因素和影响程度，建立评价脂质体稳定性的可靠方法和参数，预测制剂的储存时间才是当前研究需要解决的问题所在。     

甲氧基聚乙二醇-磷脂酰乙醇胺的制备及其对脂质体的稳定作用

采用两步反应法制备脂质体空间稳定膜材料甲氧基聚乙二醇-磷脂酰乙醇胺(MPEG—EPE)，并用以制备空间稳定脂质体(SLs)，同时制备不含MPEG—EPE的传统脂质体(CLs)，比较两者放置过程中粒径变化、加乙醇后浊度变化、包封钙黄绿素后在冻干-再水化过程中的荧光泄漏程度及其与人血浆蛋白的吸附指标，评价MPEG2000-EPE对脂质体的稳定作用。结果表明，试验前后SLs的粒径及浊度变化不大，荧光泄漏程度和人血浆蛋白吸附量也远小于CLs，提示其对脂质体有良好的稳定作用。     

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。     

修饰脂质体的可断裂聚乙二醇脂质衍生物的研究进展

聚乙二醇脂质衍生物可增加脂质体的稳定性，延长其体内循环时间。传统的长循环材料由于连接聚乙二醇与脂质的化学键太稳定，导致脂质体内容物释放延迟而影响药效。近年来提出可断裂聚乙二醇脂质衍生物的概念，该类衍生物具有可以在人的生理或病理条件下断裂的性质，能够延长脂质体体内循环时间，在到达靶部位后由于聚乙二醇已经从脂质体表面脱落，脂质体可以与病变细胞结合，从而将药物送入细胞。本文综述了可断裂聚乙二醇脂质衍生物的种类、断裂类型、在脂质体中的应用概况及在应用中的优势和局限。     

聚乙二醇单甲醚(2000)胆固醇琥珀酸酯包衣脂质体的研究

用聚乙二醇单甲醚 (2 0 0 0 )胆固醇琥珀酸酯 (PEGCHS)对脂质体进行包衣 ,以钙黄绿素(CF)为荧光探针 ,考察了不同PEGCHS加入量对脂质体包封率的影响 ,结果表明 ,随PEGCHS量的增加 ,包封率降低 .比较了包衣前后脂质体的体外、体内释放性 ,证明包衣后的脂质体 ,其体内半衰期大大延长 .     

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.     

多囊脂质体的研究进展

多囊脂质体（multivesicular liposomes，MVL）是采用贮库泡沫技术的一种新型脂质体，主要用于运载亲水性药物，弥补了普通脂质体对亲水性药物包封率低的不足。多用于局部注射给药，靶部位药物的缓释效果可长达几天至几周。现主要从多囊脂质体与普通脂质体的区别、多囊脂质体的制备及制备中需注意事项以及多囊脂质体的应用三方面对其进行综述。     

Photodynamic ultradeformable liposomes: Design and characterization

Hydrophobic ([tetrakis(2,4-dimetil-3-pentyloxi)-phthalocyaninate]zinc(II)) (ZnPc) and hydrophilic ([tetrakis(N,N,N-trimethylammoniumetoxi)-phthalocyaninate]zinc(II) tetraiodide) (ZnPcMet) phthalocyanines were synthesized and loaded in ultradeformable liposomes (UDL) of soybean phosphatidylcholine and sodium cholate (6:1, w/w, ratio), resulting 100 nm mean size vesicles of negative Zeta potential, with encapsulation efficiencies of 85 and 53%, enthalpy of phase transition of 5.33 and 158 J/mmol for ZnPc and ZnPcMet, respectively, indicating their deep and moderate partition into UD matrices. Matrix elasticity of UDL-phthalocyanines resulted 28-fold greater than that of non-UDL, leaking only 25% of its inner aqueous content after passage through a nanoporous barrier versus 100% leakage for non-UDL. UDL-ZnPc made ZnPc soluble in aqueous buffer while kept the monomeric state, rendering singlet oxygen quantum yield (Φ_Δ) similar to that obtained in ethanol (0.61), whereas UDL-ZnPcMet had a four-fold higher Φ_Δ than that of free ZnPcMet (0.21). Free phthalocyanines were non-toxic at 1 and 10 μM, both in dark or upon irradiation at 15 J/cm² on Vero and J-774 cells (MTT assay). Only liposomal ZnPc at 10 μM was toxic for J-774 cells under both conditions. Aditionally, endo-lysosomal confinement of the HPTS dye was kept after irradiation at 15 J/cm² in the presence of UDL-phtalocyanines. This could lead to improve effects of singlet oxygen against intra-vesicular pathogen targets inside the endo-lysosomal system.     

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。     

恶丙嗪脂质体的制备

目的:制备恶丙嗪脂质体.方法:采用薄膜分散法制备脂质体.结果:通过正交实验筛选出优化处方.结论:我们制备出了稳定、载药量较大、包封率较高脂质体.     

Strategies for triggered drug release from tumor targeted liposomes

Introduction: Long circulating liposomal drug carriers are widely used in experimental cancer therapy because they avoid excretion and benefit from the enhanced permeability and retention-effect to accumulate at the tumor site while simultaneously limiting systemic exposure to the cytotoxic drug due to their high stability. A drawback of the stability of the formulation is that the unloading of the drug at the target site is very poor. This opens up a new challenge to trigger drug release at the target site, while still retaining most of the drug inside the carrier while it resides in the bloodstream.

Areas covered: A short introduction is given about lipid polymorphism and phase behavior. To illustrate how this can be used to design triggered release systems, the development of delivery systems that are activated by tumor environment, UV or visible light and mild heat are discussed. The most recent triggered release systems have evolved even further, creating a need for more sophisticated triggers, which are as non-invasive and patient friendly as possible.

Expert opinion: Currently the most promising triggered release systems that have advanced furthest are thermosensitive liposomal delivery systems. As mild hyperthermia also increases tissue permeability it appears a suitable trigger for drug release while it also assists in drug accumulation. Combined with an advanced imaging system in the MR-high intensity focused ultrasound, this could be the combination of delivery system and trigger that can achieve clinical success.