脑靶向给药技术研究进展

目的了解目前国内外脑靶向给药技术。方法通过文献查阅对药物通过血脑屏障方式进行综述。结果与结论尽管脑靶向给药技术还不尽完善,但目前的研究已展现其实用性和重要意义。     

脑靶向给药的研究进展

通过查阅国内外相关文献,总结了近年来脑靶向给药的研究进展,为研制趋脑性给药系统及可透过血-脑屏障治疗中枢神经系统疾病的药物提供理论参考。初步探讨了脂质体、药质体、化学传递系统和磁性靶向给药的概念、应用与评价。     

脑靶向鼻腔给药的研究进展

目的阐述鼻腔的生理特点和药物由鼻黏膜转运入脑的机制及其影响因素。方法依据近年来的29篇中外文文献,对药物的鼻腔脑靶向实验手段、离体在体模型、鼻黏膜的毒性等方面的研究进展进行阐述。结果鼻黏膜给药途径在脑内递药领域具有独特优势,其在脑部疾病治疗方面具有独到之处,值得进一步深入研究。结论药物的鼻腔脑靶向给药将受到越来越多的关注。     

跨血脑屏障靶向递药系统研究进展

脑组织局部及相关疾病的药物治疗一直是一个难题,由于血脑屏障的存在,一方面保护了脑组织免于各种有害物质的损伤,但另一方面也增加了药物到达治疗部位的难度。随着脑部疾病发病率增加,加上其较高的致残率和致死率,药物的脑靶向递送成为目前研究的一个热点。本文主要综述近年来药物脑靶向递送相关领域的研究进展。     

环糊精在靶向给药系统中的应用

近年来,为了设计一种能在特殊器官、组织和细胞等部位集中有效释放药物的新型给药系统,国内外药剂工作者做了不懈的努力,其中利用环糊精(CD)制备靶向给药系统的研究也日渐增多。由于CD包合物在水中处于主客分子动态平衡状态,它的解离程度依赖于包合物稳定常数的大小。在吸收部位,包合物解离成游离的CD和药物分子,只有游离的药物分子能够进入体循环。然而,当我们需要将药物靶向定位的时候,这种包合平衡现象往往存在其不利之处,因为当药物到达靶器官或靶组织之前包合物往往已经解离了。为了有效阻止这种解离,国外文献报道最多的是将药物结…     

跨血脑屏障纳米给药系统载体的研究进展

目的:为深入研究和开发治疗脑部疾病的药物提供参考。方法:以"血脑屏障""纳米给药系统""脑靶向""纳米药物""载体""Blood brain barrier""Brain targeting""Drug delivery system""Nanomedicine""Carrier"等为关键词,组合查询2001-2016年在Pub Med、Elsevier、中国知网、万方、维普等数据库中的相关文献,对跨血脑屏障(BBB)纳米给药系统载体的研究成果进行综述。结果与结论:共检索到相关文献242篇,其中有效文献26篇。脑靶向纳米给药系统的常用载体有脂质体、聚合物胶束、聚合物纳米粒、树枝状聚合物及固体脂质纳米粒。将脑靶向纳米载体系统用于脑部疾病对于诊断和治疗疾病意义重大,其能在一定程度上克服BBB阻碍作用,有很好的应用前景。但脑靶向纳米给药系统大多数仍停留在基础研究层面,在研究中仍存在着多种问题。今后应寻找BBB选择性更高的作用靶点,研发高效、低毒的跨BBB纳米药物。     

脑靶向空间稳定免疫脂质体研究进展

介绍了脑靶向空间稳定免疫脂质体制剂的研究进展。大部分药物因其水溶性或分子质量超过500u无法透过血脑屏障，而脑靶向空间稳定免疫脂质体能将治疗药物通过相关单抗主动靶向脑部，从而提高脑内药物浓度，降低毒副作用。     

脑靶向给药方式及研究进展

血脑屏障（BBB）是一层连续的、覆盖在99％脑毛细血管表面的内皮细胞膜,由三部分组成：最内层是脑毛细血管内皮细胞及其之间的紧密连接,中间层为基质和周细胞,最外层是星形胶质细胞和细胞外基质。脑毛细血管内皮细胞间的紧密连接和彼此间的互相重叠（物理性）、     

脑靶向给给药载体的研究进展

目的:介绍近年来国内外脑靶向给药栽体的研究进展及应用.方法:查阅近年的国内外文献,进行分析和整理.结果:综述了目前研究较多的受体介导转运载体、吸附介导转运载体、基因载体、内源性物质栽体及药剂学修饰等载体的特点及应用.结论:新的脑靶向给药载体的研究将极大地促进脑部疾病治疗的发展.     

大分子药物的脑靶向给药研究进展

介绍了几种脑靶向给药载体,如胰岛素受体单抗、转铁蛋白受体单抗、低密度脂蛋白受体单抗、与低密度脂蛋白受体相关的合成肽Angiopep-2、膜穿透肽以及来源于病毒衣壳糖蛋白中的肽段在外源性大分子物质尤其是蛋白质的脑靶向给药中的作用及研究进展。许多对中枢神经系统疾病具有潜在治疗作用的活性物质因其分子质量较大,脂溶性不佳而难以穿过血脑屏障发挥药效。血脑屏障中存在多种分子的受体,若以这些受体的抗体或配体为载体,则有可能实现外源性蛋白质的脑靶向转运。     

经鼻脑靶向递药系统的研究进展

鼻腔与脑在解剖生理上的独特联系使得鼻腔给药作为脑内递药途径成为可能.鼻腔给药作为脑靶向的途径之一,可有效地使通过其他给药途径不易透过血脑屏障的药物绕过血脑屏障到达脑部,为中枢神经系统疾病的治疗提供了一种极有发展前景的脑内递药途径.就鼻腔给药脑靶向的依据、影响因素、评价方法、剂型等方面对经鼻脑靶向递药系统的研究现状进行总结.     

Advances in brain drug targeting and delivery: limitations and challenges of solid lipid nanoparticles

Introduction: With the advancement in the field of medical colloids and interfacial sciences, the life expectancy has been greatly improved. In addition, changes in the human lifestyle resulted in development of various organic and functional disorders. Central nervous system (CNS) disorders are most prevalent and increasing among population worldwide. The neurological disorders are multi-systemic and difficult to treat as portal entry to brain is restricted on account of its anatomical and physiological barrier.

Areas covered: The present review discusses the limitations to CNS drug delivery, and the various approaches to bypass the blood brain barrier (BBB), focusing on the potential use of solid lipid nanoparticles (SLN) for drug targeting to brain. The methods currently in use for SLN production, physicochemical characterization and critical issues related to the formulation development suitable for targeting brain are also discussed.

Expert opinion: The potential advantages of the use of SLN over polymeric nanoparticles are due to their lower cytotoxicity, higher drug loading capacity and scalability. In addition, their production is cost effective and the systems provide a drug release in a controlled manner up to several weeks. Drug targeting potential of SLN can be enhanced by attaching ligands to their surface.     

经鼻脑靶向给药系统研究进展

由于血脑屏障的存在,血液中的药物难以进入中枢神经系统.近些年研究表明,经鼻腔给药后,药物可以绕过血脑屏障直接进入脑部,而且其对机体的损伤和副作用都较小,因此经鼻脑靶向给药系统不断受到更多人的关注.首先探讨了药物经鼻入脑的通路及机制,并针对鼻腔给药的不同影响因素提出了相应的优化方案,还介绍了脑靶向性的评价方法,为进一步研究鼻脑靶向制剂提供了参考.     

靶向递释系统的研究进展

靶向递释系统(targeting drug delivery system,TDDS)能够选择性作用于病变部位,控制药物的分布与释放,提高药效和降低毒副作用,已成为癌症等疾病治疗领域的研究热点之一。本文综述了各类TDDS的机制、载体类型、制备技术和体内外靶向性,对近年来靶向递释系统的研究现状、未来产品研发与临床应用的可行性进行了探讨。     

Peptide-mediated drug delivery across the blood-brain barrier for targeting brain tumors

Introduction: Transportation of the nutrients and other substances from the blood to the brain is selectively controlled by the brain capillary endothelial cells that form a restrictive barrier, so-called blood-brain barrier (BBB). Currently, there is no unimpeachable approach to overcome the BBB obstructiveness because the existing options are either invasive or ineffective.

Areas covered: This review delineates the biological impacts of BBB on brain drug delivery and targeting. The nanoscaled multifunctional shuttles armed with the targeting entities (e.g., antibodies and peptides) are discussed. Important insights are remarked into the combinatorial screening methodologies used for the identification of de novo peptides capable of crossing BBB and targeting the brain.

Expert opinion: Depending on the physicochemical properties of small molecules and macromolecules, they may cross the BBB and get into the brain either through passive diffusion or active/facilitated transportation and transcytosis in a very selectively controlled manner. Phage-derived shuttle peptides can specifically be selected against BBB endocytic machinery and used in engineering novel peptide-drug conjugates (PDCs). Nanoscaled multitargeting delivery systems encompassing PDCs can overcome the BBB obstructiveness and deliver drugs specifically to diseased cells in the brain with trivial side effects.     

Magnetic targeting for site-specific drug delivery: applications and clinical potential

Background: Magnetic vehicles are very attractive for delivery of therapeutic agents as they can be targeted to specific locations in the body through the application of a magnetic field gradient. The magnetic localization of a therapeutic agent results in the concentration of the therapy at the target site consequently reducing or eliminating the systemic drug side effects. Objective: The aim of this review is to provide an update on the progress made in the development of the magnetic targeting technique addressing characteristics of the magnetic carriers and limitations of the current targeting magnet systems. Methods: This review discusses fundamental requirements for the optimal formulation of the magnetic carrier, current applications and potentially new approaches for the magnetically mediated, site-specific localization of therapeutic agents, including drugs, genes and cells. Results/conclusion: More efficient targeting magnetic systems in combination with prolonged circulation lifespan and carriers' surface recognition properties will improve the targeting efficiency of magnetic nanocarriers and enhance therapeutic agent availability at the molecular site of agent action. The main future magnetic targeting applications were categorized emphasizing the most promising directions and possible strategies for improving the magnetic targeting technique.     

跨血脑屏障的药物递送策略研究进展

中枢神经系统（CNS）疾病是由各种复杂的缺血性、出血性、炎症性、神经退行性和发育性疾病引起的,是一类具有普遍性且治疗效果不佳的疾病。治疗CNS疾病的一个主要障碍是血脑屏障,它是一种保护大脑的、动态的、适应性强、功能高度复杂的天然屏障,许多具有治疗活性的药物被发现,但是由于其无法跨越血脑屏障,最终很难转化为有效的临床成果。综述跨血脑屏障实现药物脑递送的策略：干扰血脑屏障的紧密连接或外排系统、提高候选分子的血脑屏障透过性和载体偶联药物的脑递送,旨在为CNS药物的开发提供参考。     

The potential for nanoparticle-based drug delivery to the brain: overcoming the blood–brain barrier

The development of blood–brain barrier (BBB)-targeting technologies is a very active field of research: targeting therapeutic actives to the central nervous system by means of systemic administration means crossing the BBB, and this is now one of the most challenging problems in drug development. The BBB is a unique regulatory system that protects the brain environment by separating it from direct contact with the circulating blood. In doing so, it impedes at the same time the access of a large number of diagnostic and therapeutic agents into the brain parenchyma. One of the possibilities of bypassing this barrier relies on specific properties of nanoparticulate vectors designed to interact with BBB-forming cells at a molecular level, as a result of which the transport of drugs or other molecules (such as nucleic acids, proteins or imaging agents) could be achieved without interfering with the normal function of the brain. This article summarises several recent example applications, presents emerging work and highlights the directions for further developments in this area.     

A novel progress of drug delivery system for organelle targeting in tumour cells

Abstract

At present, malignant tumours have become one of the most serious diseases that endanger human health. According to a survey on causes of death in Chinese population in early 1990s, the malignant tumours were the second leading cause of death. In the treatment of tumours, the ideal situation is that drugs should target and accumulate at tumour sites and destroy tumour cells specifically, without affecting normal cells and stem cells with regenerative capacity. This requires drugs to be specifically transported to the target organs, tissues, cells, and even specific organelles, like mitochondria, nuclei, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus (GA). The nano drug delivery system can not only protect drugs from degradation but also facilitate functional modification and targeted drug delivery to the tumour site. This article mainly reviews the targeting of nano drug delivery systems to tumour cytoplasmic matrix, nucleus, mitochondria, ER, and lysosomes. Organelle-specific drug delivery system will be a major mean of targeting drug delivery with lower toxicity, less dosage and higher drug concentration in tumour cells.