基因药物纳米给药系统的设计与研究进展

基因药物的传递面临着体内外稳定性差、缺乏靶向性、难入胞、在细胞内难以释放等一系列障碍和挑战。因此,要实现基因药物在体内有效传递需构建能克服这些障碍的药物传递系统。随着材料科学和纳米科技的发展,大量新型的纳米载体已被用于基因药物的传递。综述目前基因药物传递所面临的障碍和挑战,基因药物纳米给药系统的设计思路及研究进展。     

纳米磁靶向药物载体在肿瘤治疗中的研究进展

纳米磁靶向药物载体是靶向治疗的一种载体形式,粒径在1~1000nm之间,它借助于磁场使药物载体聚集在靶部位,平稳释放药物,提高靶部位药物浓度,增强治疗效果,同时减少其它部位的药物分布,降低药物的毒副作用。该药物载体一方面具有磁靶向药物载体的一般特性,结合固定磁场或交变磁场而具有靶向性或产热性,携带化疗药物或放射性物质,能杀灭肿瘤细胞;另一方面粒径达到纳米级,并具有体内长循环等特性。本文介绍纳米磁靶向药物载体在肿瘤治疗(包括化疗、放疗、热疗等)领域的研究进展。1纳米磁靶向药物载体在肿瘤化疗中的应用纳米磁靶向药物载体能携…     

纳米药物在青光眼治疗中的研究进展

目的:了解纳米药物在青光眼治疗中的应用进展。方法:查阅近年来国内外相关文献,从降眼压、保护视神经和抗纤维化等作用方面对治疗青光眼的纳米药物的研究进行归纳和总结。结果与结论:纳米药物有角结膜透过率高、眼表作用时间长、长期缓释和靶向性好等优点,可有效解决青光眼药物治疗中的眼后节靶向给药和蛋白类药物长效释放等难题,并减少防腐剂造成的眼表毒性。在保护视神经方面,纳米药物可以为基因或蛋白类药物提供高效载体,实现细胞靶向的缓控释给药。对于青光眼术后的抗纤维化治疗,纳米药物可显著降低药物的毒副作用,有效减少并发症的发生。以纳米药物为载体的青光眼基因治疗相对于病毒载体有着更好的安全性和有效性,展现出良好的应用前景。     

非病毒基因递送载体的研究进展

目前,基因药物的递送成为药学研究的热点,基因递送载体主要包括病毒载体和非病毒载体。非病毒基因载体的毒性低,生物相容性好,转染效率高,具有潜在的临床应用价值。本文就靶向递送基因载体、多功能基因载体、同时载基因与化疗药物的载体、智能基因载体和脂质体等非病毒基因递送载体的研究进展做一综述。     

还原响应型药物载体的研究进展

还原响应型药物载体以其高效快速释放药物、毒副作用小、可生物降解的优良特性,逐渐成为药物载体领域研究的热点,也是最具临床应用潜力的智能药物载体之一。本文综述了还原响应型药物载体研究的最新进展,包括还原响应的药物、基因与载体的偶联物及还原响应的纳米聚合物胶束、纳米囊泡、纳米中空微球、纳米脂质体等的合成和药物释放的机制以及各类载体的优缺点,为其在药剂学中的进一步应用提供理论依据。     

纳米粒淋巴靶向的研究进展

目的从淋巴靶向方面综述脂质体、纳米活性炭以及纳米碳管纳米粒的研究进展。方法参考近年来32篇相关的中外文献,在淋巴系统的生理基础上,探讨上述纳米粒的淋巴靶向性及其在淋巴靶向方面的应用。结果脂质体具有天然的淋巴靶向性。纳米活性炭有较好的淋巴趋向性,并能在淋巴结处缓缓释放出药物。纳米碳管可通过表面修饰来提高其淋巴靶向性。上述纳米粒均可以作为显影剂与药物载体以提高其淋巴靶向性。结论纳米粒有较好的淋巴靶向性,可以作为显影剂和药物靶向淋巴的理想载体。     

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。     

壳聚糖在药物制剂中的应用研究进展

综述壳聚糖在生物大分子口服给药、pH敏感释药、靶向给药、纳米药物载体等药物制剂方面的应用研究进展。     

pH敏感型纳米递药系统在肿瘤靶向治疗中的作用

目的 综述目前pH敏感纳米递药系统用于肿瘤靶向治疗中的国内外研究进展。方法 在Pubmed和Google上检索近年国内外资料,阐明pH敏感纳米递药系统靶向肿瘤治疗的作用机制,对超顺磁性纳米粒、胶束、树状大分子等相关研究成果进行总结和评价。结果 传统肿瘤化疗药物普遍存在疗效低、副作用大等问题,而近年来研发的pH响应的纳米载体可通过EPR效应积聚于肿瘤组织,并在弱酸性的肿瘤细胞外液或经内吞作用后在细胞质或溶酶体中释放药物。该pH敏感型载体能促进药物的靶向递送,在减少系统性副作用的同时提高肿瘤化疗疗效。结论 pH敏感纳米递药系统在肿瘤靶向治疗中具有广阔的应用前景,开发具有靶向性、高效性、安全性的递药系统是目前该领域研究主要方向之一。     

纳米药物研究进展及前景展望

纳米药物与普通制剂的药物相比,具有较大的表面积、较强的化学活性、较快的吸收速度,在通过生物体的各种屏障、控制药物的释放速度、设定药物的靶向性等许多方面,纳米药物都具有一般药物不可替代的优越性,为药物研究提供了全新的领域。本文从纳米药物的制备、特点、应用等几方面介绍纳米药物的研究进展并展望了纳米药物的前景。     

纳米载体应用于透皮给药系统的研究进展

纳米载体经皮给药系统是近几年经皮给药的研究热点。本文综述了各种纳米载体在经皮给药系统中应用的研究进展,其中囊泡、微乳和固体脂质纳米粒作为经皮给药载体已得到相对深入的研究,而新型纳米载体如胶束、树状大分子和细胞促透多肽等尽管研究较少,但基于其明显的促渗作用,将会为经皮给药系统的研究提供新方向。     

Recent advances in bacterial therapeutics based on sense and response

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.     

The features and shortcomings for gene delivery of current non-viral carriers

Since the viral vector for gene therapy has serious problems, including oncogenesity and other adverse effects, non-viral carriers have attracted a great deal of attention. Non-viral carriers are expected to achieve gene therapy without serious side effects. However, the most critical issue of gene delivery by non-viral carriers is the low-expression efficiencies of the desired gene. In order to apply non-viral carriers for gene therapy in practical clinical usage, further understanding of the cellular barriers against gene delivery is a prerequisite. Moreover, additional intelligent concepts for gene delivery are also needed. We will summarize the features and shortcomings of currently developed non-viral delivery systems. Especially, we will address the current progress of cationic lipids (lipoplex) and cationic polymers (polyplex) in terms of transfection efficiency. Furthermore, our group has developed a system that responds to the particular intracellular signals of target disease cells. We have named this gene delivery system a drug delivery system based on responses cellular signal (D-RECS). We will introduce this new concept of intelligent non-viral delivery system that our group recently developed.     

Capture of magnetic carriers within large arteries using external magnetic fields

Our overall research goal is to advance the safety and effectiveness of acute ischemic stroke therapy by improving the benefit/risk ratio of thrombolysis and hence, the long-term outcome of acute ischemic stroke victims. Our approach is the development of a novel tissue plasminogen activator (t-PA) delivery system based on t-PA-loaded magnetic nano- and microcarriers guided directly to the site of vascular occlusion by external magnetic fields. Such a t-PA delivery system would conveniently combine the advantages of both intravenous (systemic) and intraarterial (catheter-facilitated) thrombolysis: non-invasiveness - the magnetic t-PA carriers can be injected intravenously and targeted, as drug delivery is magnetically guided to and t-PA focally released at and within the vascular clot to induce lysis. The focus of our discussion are the two necessary, fundamental and interrelated bioengineering steps: the research and development of well-characterized, biocompatible, functionally active and t-PA-loaded (encapsulated) magnetic nano- and microcarriers able to induce effective thrombolysis, and the design of magnetic guidance systems for targeted tPA-delivery allowing also the triggered release of the thrombolytic agent at the clot site. In this paper, we theoretically demonstrated magnetic trapping of blood borne magnetic nano- and microcarriers from human large vessels, especially arteries. Then, some preliminary experiments using primate models (monkeys) were done to identify successful in vivo sequestration of magnetic carriers in large and smaller arterial branches after arterial upstream and systemic venous injection. Histology (hematoxylin-eosin stain) verified intraarterial carrier concentration (identified as black carrier agglomerates on H and E staining) at the arterial region above the surface magnet. The results revealed the feasibility of magnetic drug-targeting at arteries and solidified the proposed t-PA delivery system.     

Chemical robotics — chemotactic drug carriers

In this review we show and describe a concept of designing autonomously moving artificial cells (chemical robots) carrying drugs and having tactic behavior based on artificial chemotaxis. Such systems could help to provide new and more efficient drug delivery applications. Chemical robot can be constructed based on the self-organization — natural “bottom-up” way — of fatty acid or lipid molecules into ordered nano- or micrometer size objects that have the ability to move and respond to environmental stimuli. The idea of using tactic carriers in drug delivery applications can be justified by the fact that cancer sites in the living body have different physiological characters (lower pH and higher resting temperature) compared to normal cells. The proposed “bottom-up” design method for self-propelled objects at small scales for targeted drug delivery applications could realize the original designation of nanoscience proposed 50 years ago by Richard Feynman.     

Disease-responsive drug delivery: the next generation of smart delivery devices

With the advent of highly potent and cytotoxic drugs, it is increasingly critical that they be targeted and released only in cells of diseased tissues, while sparing physiologically normal neighbors. Simple ligand-based targeting of drug carriers, although promising, cannot always provide the required specificity to achieve this since often normal cells also express significant levels of the targeted receptors. Therefore, stimuli-responsive delivery systems are being explored to allow drug release from nano- and microcarriers and implantable devices, primarily in the presence of physiological or disease-specific pathophysiological signals. Designing smart biomaterials that respond to temperature or pH changes, protein and ligand binding, disease-specific degradation, e.g. enzymatic cleavage, has become an integral part of this approach. These strategies are used in combination with nano- and microparticle systems to improve delivery efficiency through several routes of administration, and with injectable or implantable systems for long term controlled release. This review focuses on recent developments in stimuli-responsive systems, their physicochemical properties, release profiles, efficacy, safety and biocompatibility, as well as future perspectives.     

聚合物胶束作为药物载体及其在肿瘤靶向方面的研究进展

聚合物胶束具有粒径小、稳定性高、滞留时间长、良好的生物相容性等特点,这些优良性质使得聚合物胶束作为药物载体具有许多独特的优势。近年来,涌现了许多围绕聚合物胶束设计肿瘤靶向给药系统的报道,包括利用肿瘤的病理学性质,设计被动靶向给药系统和对聚合物胶束进行表面修饰,设计主动靶向给药系统。本文主要综述了聚合物胶束作为肿瘤靶向药物载体的研究进展。     

壳聚糖在新型给药系统中的应用

综述壳聚糖的物理化学和生物特性及在基因转染和不同给药系统中的应用研究近况。壳聚糖作为新型药用辅料,已受到越来越多的关注,对其应用的开发和研究已渗透到药剂学的多个领域。壳聚糖用作非病毒基因载体,也已成为近年来的研究热点之一。它也被广泛研究应用于眼部、鼻腔、口腔、胃内、小肠和结肠等靶向给药载体。     

Thermoresponsive polymers as gene and drug delivery vectors: architecture and mechanism of action

Introduction: This topic is important as it allows for improved specificity in drug delivery, providing possibilities for reduced side effects, and thereby improved pharmacotherapy. As a wealth of different polymers and mechanisms of action has been suggested, a systematic overview of the field is of current importance.

Areas covered: This article presents an overview over a selection of thermoresponsive polymers suitable as excipients in systems for gene and drug delivery with particular emphasis on the influence of polymer structure, composition, molecular weight (MW) and architecture on the responsive mechanisms. Due to the immense number of reports on these increasingly popular materials, focus has been restricted to the use of micelle-forming polymers with a lower critical solution temperature, temperature-responsive hydrogels for drug delivery applications and temperature-sensitive polymers as non-viral vectors for polynucleotide delivery. Specific examples covered are poly-(N-isopropylacrylamide) (PNIPAAM), Pluronics and their derivatives. It is concluded that the studies constitute an excellent platform for development of thermoresponsive systems with improved gene and drug delivery properties.

Expert opinion: A thorough knowledge of factors important for loading efficiency and drug release is necessary to be able to develop optimal nano-carriers for the future. Other issues that are not fully understood is how small the carriers need to be, and which manufacturing procedures should be used.