共查询到20条相似文献,搜索用时 78 毫秒
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RNA干扰(RNA interference,RNAi),是一种在动植物中存在的通过双链RNA诱导同源特异性序列转录后基因沉默的过程。虽然小干扰RNA (siRNA) 较单链反义寡核苷酸显示出更好的稳定性与基因沉默效果,但是作为新型的基因治疗药物,靶向递送siRNA是药物进入临床应用最主要的环节,siRNA体内有效作用发挥的关键在于它在体内能否高效递送至靶细胞并与靶基因结合。目前研究主要集中在siRNA的修饰方式与递送载体研究,以提高其体内的稳定性与靶向性。文中主要综述了siRNA的体内靶向递送障碍以及近几年siRNA非病毒递送载体脂质体、阳离子多聚物、纳米粒、胶束等方面的研究进展。 相似文献
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信使核糖核酸(messenger ribonucleic acid,mRNA)作为一种非常有潜力的基因药物,在蛋白质替代疗法、疫苗、基因编辑等方面具有广阔的应用前景。而安全高效的mRNA递送系统是其临床转化成药的关键。脂质和聚合物载体因其结构多样、制备简便等优势,被广泛用于mRNA递送。两者均能有效负载mRNA并保护其不被降解,促进其被靶细胞摄取,快速逃逸并释放mRNA,提升mRNA递送效率。通过对不同类型脂质和聚合物载体在mRNA递送中研究进展进行综述,以期为后续设计新型mRNA递送载体提供思路及参考。 相似文献
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目的: 了解国内外对于可溶性聚合物微针这一新型药物递送系统的研究进展,并对其优势及存在的问题进行分析,对发展前景进行展望。方法: 通过文献调研,总结可溶性聚合物微针的材料及功能,分析可溶性微针所解决的临床用药问题,以及各微针基质材料所具有的优势与面临的挑战。结果: 本文以临床不同的用药需求为视角进行分类,介绍了聚合物材料在可溶性微针递药系统中的应用,并对其优势及面临的挑战进行总结,对发展前景进行展望。结论: 目前对于可溶性聚合物微针的研究已取得了令人瞩目的进展。然而,为实现临床转化,可溶性聚合物微针递药系统的载药能力、安全性等方面仍然需要进一步的研究。 相似文献
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目的:为开发新型纳米微粒系统用于体内递送小干扰RNA(siRNA)提供参考。方法:总结siRNA体内递送障碍并综述近年来纳米微粒系统介导siRNA体内递送的研究现状。结果与结论:siRNA需要解决肾滤过、吞噬细胞摄取、血清蛋白凝聚以及内源性核酸酶降解等障碍。聚乳酸-乙醇酸共聚物纳米微粒系统能有效包载siRNA,改善其体内稳定性,但存在内含体逃逸及不能及时释放siRNA的缺陷;壳聚糖纳米微粒系统包载siRNA稳定性高、包封率达83%~94%、基因沉默效率接近80%;环糊精纳米微粒系统包载siRNA未见严重毒副作用;胶束纳米微粒系统能有效保护siRNA免受核酸酶降解,并能适时释放siRNA;阳离子共聚物纳米微粒系统能有效防止siRNA被核酸酶降解,但转染效率低;脂质纳米微粒系统可显著提高siRNA对靶基因的沉默效果,但存在一定毒性及易引起siRNA脱靶效应。部分荷载siRNA的纳米微粒系统用于临床试验已得到了令人鼓舞的成果,但仍有较多问题亟待解决。联合应用多种递送系统传送siRNA可能是未来研究发展趋势。 相似文献
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小干扰RNA(siRNA)是一个靶向治疗和精确医学的代表性治疗工具,可通过序列特异性的RNA干扰(RNAi)沉默任何疾病相关基因的表达。然而,它的治疗前景历来受到体内半衰期短、递送困难和安全问题的限制。非病毒载体介导的药物递送已经成为克服这些局限性的一个成功策略,可实现siRNA在体内的有效递送,高效沉默靶基因。目前,已有多种药物处于临床试验中,4种基于siRNA的新型疗法已获得美国FDA的批准,标志着靶向疗法新时代的开始。该文概述了近年来基于siRNA的非病毒载体递送策略的新进展及其应用,并展望了siRNA药物研究的未来发展趋势。 相似文献
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《中国药房》2017,(31):4452-4455
目的:为小干扰RNA(siRNA)纳米制剂递送的研究提供参考。方法:以"基因治疗""RNA干扰""小干扰RNA""载体系统""siRNA""Gene therapy""RNA interference""Protamine"等为关键词,组合查询1996-2016年在PubMed、中国知网、万方、维普等数据库中的相关文献,对载siRNA的纳米制剂的导入方法、载体类型及影响递送过程的主要因素进行综述。结果:共检索到相关文献500余篇,其中有效文献40篇。载siRNA的纳米制剂导入方法主要分为物理化学法和载体介导法。在载体介导法中的非病毒载体,不仅克服了siRNA半衰期短、生物利用度低等缺点,而且在一定程度上提高了siRNA的递送效率,是现代药剂学研究的一个热点。常用非病毒载体包括阳离子脂质体、二元复合物纳米载体、三元复合物纳米载体。载体靶向性修饰、粒径与表面电荷是递送siRNA纳米载体主要影响因素。siRNA的高效递送依赖于新的高效、低免疫原性载体的开发以及纳米制剂递送系统的优化。因此,可载siRNA的高效、低免疫原性纳米制剂的研究任重而道远。 相似文献
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骨骼是人体重要的组成部分,随着人口老龄化以及肿瘤高发,骨相关疾病已经严重影响患者的生活质量。全身给药治疗骨类相关疾病存在靶向性差、副作用大、药物利用度低等缺点。骨靶向递药系统有效克服了传统给药方式治疗骨类相关疾病的缺陷,利用骨靶向基团对药物载体进行功能化修饰可有效提高药物疗效,降低成本,并减少不良反应。综述通过查阅相关文献,对近几年骨靶向系统的研究进展进行了归纳总结,介绍了骨靶向系统中骨靶向基团与纳米载体的应用,为骨靶向药物递送系统的深入研究开拓了新的思路。 相似文献
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《Asian Journal of Pharmaceutical Sciences》2018,13(6):592-599
Gene therapy using siRNA molecules is nowadays considered as a promising approach. For
successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral
and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack
of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low
nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls
of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides
an abundance of amino-groups for loading of a larger amount of siRNA molecules
via electrostatic adsorption. After loading, the particles were covered with a second layer
of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective
cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered
siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate
that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared
to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified
MSNs can be considered as prospective vectors for therapeutic siRNA delivery. 相似文献
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Yumei Wu Yuanyuan Liu Xinyue Li Dereje Kebebe Bing Zhang Shouying Du Zhido 《Asian Journal of Pharmaceutical Sciences》2019,14(1):1-15
Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (<5%). The designing of a novel approach for a safe, simple, and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem. Over the past decades, several novel approaches involving different strategies have been developed to improve the ocular delivery system. Among these, the ophthalmic in-situ gel has attained a great attention over the past few years. This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system. 相似文献
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H. de Martimprey C. Vauthier P. Couvreur 《European journal of pharmaceutics and biopharmaceutics》2009,71(3):490-504
The success of the application of new therapeutic methods based on RNA interfering strategies requires the in vivo delivery of active ODN or siRNA down to the intracellular compartment of the target cells. This article aims to review the studies related to the formulation of RNA interfering agents in polymer nanocarriers. It will present the different types of polymer nanocarriers used as well as the biological activity of the resulting ODN and siRNA loaded nanocarriers. As will be explained, the part of the in vitro studies provided useful data about the intracellular delivery of the formulated RNA interfering agents. Investigations performed in vivo have considered animal models of different relevant diseases. Results from these investigations have clearly demonstrated the interest of several polymer nanocarriers tested so far to deliver active RNA interfering effectors in vivo making possible their administration by the intravenous route. 相似文献
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Bioerodible polymers have been extensively used as carriers for drug delivery and as scaffolds for tissue engineering. The ability to model and predict erosion behavior can enable the rational design and optimization of biomaterials for various biomedical applications in vivo. This review examines critically the current approaches in mathematical modeling of the erosion of synthetic polymers. The models are classified broadly based on whether they use phenomenological, probabilistic, or empirical approaches. An analysis of the various physical, chemical, and biological factors affecting polymer erosion and the classes of bioerodible polymers to which these analyses have been applied are discussed. The key features and assumptions associated with each of the models are described, and information is provided on the limitations of the models and the various approaches. The review concludes with several directions for future models of polymer erosion. 相似文献
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Kamal Dua Ridhima Wadhwa Gautam Singhvi Vamshikrishna Rapalli Shakti Dhar Shukla Madhur D. Shastri Gaurav Gupta Saurabh Satija Meenu Mehta Navneet Khurana Rajendra Awasthi Pawan Kumar Maurya Lakshmi Thangavelu Rajeshkumar S Murtaza M. Tambuwala Trudi Collet Philip M. Hansbro Dinesh Kumar Chellappan 《Drug development research》2019,80(6):714-730
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Irfan Ullah Kunho Chung Jagadish Beloor Jongkil Kim Minyoung Cho Nahyun Kim 《Journal of drug targeting》2017,25(4):320-329
siRNA entrapment within endosomes is a significant problem encountered with siRNA delivery platforms that co-opt receptor-mediated entry pathways. Attachment of a cell-penetrating peptide (CPP), such as nona-arginine (9R) to a cell receptor-binding ligand like the Rabies virus glycoprotein, RVG, allows effective siRNA delivery to the cytoplasm by non-endocytic pathways, but a significant amount of siRNA complexes also enters the cell by ligand-induced receptor endocytosis and remain localized in endosomes. Here, we report that the incorporation of trileucine (3 Leu) residues as an endo-osmolytic moiety in the peptide improves endosomal escape and intracellular delivery of siRNA. The trileucine motif did not affect early non-endosomal mechanism of cytoplasmic siRNA delivery but enhanced target gene silencing by?>20% only beyond 24?h of transfection when siRNA delivery is mostly through the endocytic route and siRNA trapped in the endosomes at later stages were subject to release into cytoplasm. The mechanism may involve endosomal membrane disruption as trileucine residues lysed RBCs selectively under endosomal pH conditions. Interestingly?<3 Leu or?>3 Leu residues were not as effective, suggesting that 3 Leu residues are useful for enhancing cytoplasmic delivery of siRNA routed through endosomes. 相似文献