脑肿瘤靶向纳米递药系统的研究进展

脑肿瘤中恶性肿瘤较为常见,脑瘤发展快、治疗难导致了较高的死亡率。采用化学药物治疗时,药物进入脑肿瘤组织必须通过血脑屏障和血- 脑瘤屏障。一些有潜力的抗肿瘤药物由于自身物理化学性质的限制,不能有效到达肿瘤。针对脑肿瘤形成和发展不同阶段的特点,目前脑肿瘤靶向递药有3 种策略：跨血脑屏障（BBB）转运递药、跨血- 脑瘤屏障（BBTB）转运递药和利用实体瘤的高通透性和滞留效应（EPR 效应）递药,已被广泛研究的纳米递药载体有脂质体、固体脂质纳米粒、聚合物胶束、树枝状聚合物、碳纳米管、聚合物纳米粒、磁性纳米粒等。控制载药纳米微粒粒径大小以及对其表面进行修饰可改善药物在体内的分布与滞留,提高化疗药物的疗效,降低毒副作用。多级靶向纳米递药系统有潜力成为治疗脑肿瘤的重要辅助方式。     

多功能纳米载体

目前所用药物纳米载体（如脂质体，胶束，纳米乳，聚合物纳米粒）有很多有益特性，如血液循环时间延长，使药物在痛灶聚集；靶向作用；增强细胞内渗透作用；体内载体造影；生理环境敏感的药物释放。但多功能纳米载体仍很少，如长循环免疫脂质体。多功能药物纳米载体可显著增强许多治疗和诊断试剂的效果。本文论述了多功能纳米载体的当前状况和发展方向，主要关注结合长循环性、靶向性、胞内渗透性和造影能力的多功能纳米载体。     

长循环纳米粒与肿瘤的细胞靶向研究进展

可用作抗肿瘤药物研究中的载药纳米粒包括脂质体、聚合物胶束、脂复合物及一些聚合物。为保证纳米粒的成功靶向,需要延长其在血液中的循环时间。长循环纳米粒可以达到这一效果,其最常用的修饰聚合物是聚乙二醇（PEG）。这一类聚合物可以将粒子表面隐藏起来,从而“躲过”,单核吞噬细胞系统（MPS）的吸收和血浆蛋白的调理,增加在血液中的循环时间,达到缓释的效果。与此同时,纳米粒在到达病理靶部位时,将采取一定方式裂解、释药或直接与肿瘤细胞结合并内化,达到控释效果。起到相应的治疗作用,本文就长循环纳米粒靶向肿瘤细胞这方面的相关研究做一综述。     

叶酸受体介导的肿瘤靶向纳米递药系统

叶酸受体在上皮源性的恶性肿瘤细胞膜表面高度表达。叶酸靶向纳米递药系统具有叶酸-叶酸受体主动靶向和纳米递药系统被动靶向的双重优势,可实现化疗药物对肿瘤组织的靶向递送,有效提高药物疗效,减少毒副作用。本文就近年来研究较多的叶酸-脂质体、叶酸-树枝状聚合物、叶酸-聚合物胶束、叶酸-纳米球等叶酸受体介导的肿瘤靶向递药系统进行综述。     

天然药物靶向给药系统的研究

采用新型药物载体使天然药物具有靶向作用是近年来药剂学的研究热点之一。综述脂质体、纳米粒、微球、微乳、药质体等新型载体在天然药物靶向给药系统研究中的应用,并介绍膜融合脂质体、纳米脂质载体、药脂结合物纳米粒以及分泌颗粒类似物等几种新型靶向给药系统的药物载体。     

抗 EGFR 单克隆抗体偶联载紫杉醇纳米粒对胃癌肿瘤靶向性能力研究

目的：为了增强载药纳米粒靶向肿瘤的能力,将载药纳米粒与抗上皮生长因子细胞增殖和信号传导受体（EGFR）单克隆抗体偶联,探究该偶联是否会增加胃癌肿瘤靶向性。方法将制备好的载药纳米粒在羟基胶乳微球偶联抗体（EDC）的作用下通过酰胺反应与抗 EGFR 单克隆抗体进行偶联,制备成载药免疫纳米粒。通过透析袋法测定纳米粒体外缓释效果,用 ELISA 法测定抗体与载药纳米粒偶联率,最后采用荧光标记法对胃癌模型鼠进行活体成像结果纳米粒表面光滑,分布均匀,粒径在200～300 nm 间,载药量为61．02％,并且具有缓慢释药的效果,抗体与载药纳米粒的偶联率达到了70％,最终荧光活体成像的结果显示,此免疫载药抗体具有靶向胃肿瘤的效果。结论我们制备的免疫纳米粒既可以缓释药物也存在一定肿瘤靶向性,所以将抗体与载药纳米粒偶联,可以增加肿瘤病灶处局部的药物浓度,以此来缓解抗肿瘤药物对人体其他正常组织毒副作用。     

TAT介导的几种纳米药物载体的研究概况

TAT是一种应用最早且现今最为常用的细胞穿膜肽,已经成功与多种纳米载体如脂质体、胶束、纳米粒等连结形成可内化进入细胞内的载药体系。文章主要对TAT介导的几种纳米载药体系的穿透机制、体内外抗肿瘤活性及靶向病变部位能力等方面的研究进行综述,同时对微环境pH敏感的TAT靶向药物载体的研究进展作了简单介绍。     

PLGA纳米粒抗肿瘤药物载体的研究进展

目的：阐述近年来PLGA 纳米粒作为抗肿瘤药物载体的研究进展。方法归纳国内外最新的文献报道,对PLGA纳米粒作为抗肿瘤药物载体在主动与被动靶向方面的应用研究进展进行综述。结果由于纳米材料可以增强抗肿瘤药物的靶向作用,而PLGA是经FDA认证的具有生物降解性及生物相容性的功能高分子有机聚合物,已经被广泛地应用于抗肿瘤药物的载体研究。结论 PLGA纳米粒作为抗肿瘤药物载体具有广阔的应用前景。     

脑靶向纳米载体系统的研究进展

目的纳米载体可跨越血脑屏障靶向脑组织,提高脑内药物浓度,实现脑靶向。此文综述了脂质体、聚合物纳米粒、聚合物胶束、纳米凝胶、微乳和固体脂质纳米粒等纳米载体系统脑靶向给药的最新研究进展,并讨论了透过血脑屏障的机制。     

核-壳结构的脂质-聚合物杂化纳米粒的研究进展

核-壳结构的脂质-聚合物杂化纳米粒（CSLPHNs）是以具有生物可降解性的聚合物纳米粒为核,外层包覆单层或多层具有生物膜仿生性的脂质壳而形成,结合了纳米粒和脂质体的双重优点,具有粒径小、载药量高、生物相容性好及缓控释给药等优势,在药物递送系统中应用甚广。笔者在查阅近年国内外文献的基础上归纳了CSLPHNs的基本特性、制备方法及在眼部给药、肿瘤治疗及临床诊断成像中的最新研究进展。     

Solid lipid nanoparticles as drug delivery systems

For a decade, trials have been made to utilize solid lipid nanoparticles (SLNs) as alternative drug delivery systems to colloidal drug delivery systems such as lipid emulsions, liposomes, and polymeric nanoparticles. Various lipid matrices, surfactants, and other excipients used in formulation, preparation methods, sterilization and lyophilization of SLNs are discussed in this article. Entrapment efficiency of drug carrier and its effect on physical parameters, drug release, and release mechanisms of various compositions are reviewed and discussed. Important points in characterization and stability of SLNs are outlined. Various in vitro studies carried out by different research groups are mentioned in addition to in vivo evaluation. Exploitation potential of SLNs to administer by various routes of administration are covered. Passive and active drug targeting using SLNs are presented.     

Solid lipid nanoparticles for targeted brain drug delivery

The present review discusses the potential use of solid lipid nanoparticles for brain drug targeting purposes. The state of the art on surfactant-coated poly(alkylcyanoacrylate) nanoparticles specifically designed for brain targeting is given by emphasizing the transfer of this technology to solid lipid matrices. The available literature on solid lipid nanoparticles and related carriers for brain drug targeting is revised as well. The potential advantages of the use of solid lipid nanoparticles over polymeric nanoparticles are accounted on the bases of a lower cytotoxicity, higher drug loading capacity, and best production scalability. Solid lipid nanoparticles physicochemical characteristics are also particularly regarded in order to address the critical issues related to the development of suitable brain targeting formulations. A critical consideration on the potential application of such technology as related to the current status of brain drug development is also given.     

Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals

INTRODUCTION: Lipid nanoparticles are innovative carrier systems developed as an alternative to traditional vehicles such as emulsions, liposomes and polymeric nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured lipid carriers (NLC) show important advantages for dermal application of cosmetics and pharmaceuticals. AREA COVERED: This article focuses on the main features of lipid nanoparticles, in terms of their preparation and recent advancements. A detailed review of the literature is presented, introducing the importance of these systems in the topical delivery of drugs and active substances. EXPERT OPINION: Lipid nanoparticles are able to enhance drug penetration into the skin, allowing increased targeting to the epidermis and consequently increasing treatment efficiency and reducing the systemic absorption of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles and their biocompatible chemical nature have secured them the title of 'nanosafe carriers.' SLN and NLC represent a new technological era, which has been taken over by the cosmetic and pharmaceutical industry, which will open new channels for effective topical delivery of substances.     

Exploitation of lipid-polymeric matrices at nanoscale for drug delivery applications

ABSTRACT

Introduction: Progress in drug delivery and a better quality of life for patients, relies on the development of new and suitable drug carrier systems, with unequivocal therapeutic benefits, low systemic toxicity and reduced side effects. Lipid-polymeric nanoparticles have been explored to produce nanocarriers due to their features and applications such as high drug entrapment, physical-chemical stability and controlled release properties.

Areas covered: In this review, we describe several hybrid nanoparticles obtained from mixing a polymer with a lipid matrix. This association can potentiate the efficacy of drug delivery systems, due to the enhancement of encapsulation efficiency and loading capacity, tailoring the drug release according to the therapeutic purpose, and improving the drug uptake by targeting it to specific receptors. Contrary to lipid nanoparticles, these hybrid nanoparticles can decrease the initial burst release and promote a more sustained and localized release of the drug.

Expert Opinion: Lipid-polymeric nanoparticles are versatile vehicles for drug delivery by different administration routes in the treatment of multiple diseases. Different solid lipids, polymers, surfactants and techniques for producing these carriers have been investigated, revealing the importance of their composition to achieve optimal characteristics to drug delivery.     

表面修饰脂质纳米粒给药系统的研究进展

脂质纳米粒是一种极具潜力的新型药物传输载体,对脂质纳米粒表面修饰是近年来的研究热点。通过表面修饰的手段能有效的避免单核巨噬细胞的吞噬、延长脂质纳米粒在体内的循环时间、主动靶向于病灶部位。本文就脂质纳米粒的体内命运及脂质纳米粒表面修饰的研究进展做一综述。     

Effective in-vivo utilization of lipid-based nanoparticles as drug carrier for carvedilol phosphate

Objectives Lipid nanoparticles as carrier for oral drug administration improve gastrointestinal solubility of poorly soluble drugs and thus enhance bioavailability. However, basic drugs may undergo rapid dissolution from such solid dispersions in the stomach and precipitate in the intestine due to their higher solubility in acidic medium. Therefore, the objective of this work was to study the enhancement in bioavailability of carvedilol phosphate (basic drug) by providing an alkaline gastric environment to drug‐loaded solid lipid nanoparticles. Methods An alkaline gastric environment in rats was created and maintained with oral administration of an antacid suspension 5 min before and 30 min post dosing. Key findings The formulation administered orally exhibited enhanced bioavailability (～27%) when compared with drug suspension and sustained release behaviour when compared with formulation under ideal gastric conditions. The enhanced bioavailability is due to the presence of lipid nanoparticles as drug carrier while the sustained‐release characteristic may be attributed to the presence of antacid, which resulted in elevation of gastric pH and reduced the drug's solubility. Conclusions It may be concluded that although lipid nanoparticles can be instrumental in improving bioavailability, additional sustained release may be achieved by targeting intestinal release of basic drugs from lipid vehicles, which is possible by incorporating them into suitable enteric‐coated formulations.     

Polymeric particulate technologies for oral drug delivery and targeting: a pathophysiological perspective

The oral route for delivery of pharmaceuticals is the most widely used and accepted. Nanoparticles and microparticles are increasingly being applied within this arena to optimize drug targeting and bioavailability. Frequently the carrier systems used are either constructed from or contain polymeric materials. Examples of these nanocarriers include polymeric nanoparticles, solid lipid nanocarriers, self-nanoemulsifying drug delivery systems and nanocrystals. It is the purpose of this review to describe these cutting edge technologies and specifically focus on the interaction and fate of these polymers within the gastrointestinal system.     

Perspectives on cutting-edge nanoparticulate drug delivery technologies based on lipids and their applications

Numerous nanotech arenas in therapeutic biology have recently provided a scientific platform to manufacture a considerable swath of unique chemical entities focusing on drugs. Recently, nanoparticulate drug delivery systems have emerged to deliver a specific drug to a specified site. Among all other carriers, lipids possess features exclusive to nanostructured dosage forms. The bioavailability of orally administered drugs is typically negatively affected by their poor water solubility, resulting from the unique chemical moieties introduced. Because of their unique advantages, lipid nanoparticles must become increasingly predictable as a robust delivery mechanism. The enhanced biopharmaceutical properties and significance of lipid-based targeting technologies such as liposomes, niosomes, solid lipid nanoparticles and micelles are highlighted in this review. Pharmaceutical implications of lipid nanocarriers for the transport and distribution of various therapeutic agents, such as biotechnological products and small pharmaceutical molecules, is a booming topic. Lipid nanoparticles as drug delivery systems have many appealing properties, including high biocompatibility, ease of preparation, tissue specificity, avoidance of reticuloendothelial systems, delayed drug release, scale-up feasibility, nontoxicity and targeted delivery. The use of lipid nanoparticles to enhance the transport of biopharmaceuticals is currently considered state-of-the-art. Similarly, we critically examine the upcoming guidelines that therapeutic scientists should handle.