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用于全身递送小干扰RNA的脂质体和脂质包膜型系统

Liposomes and Lipid Envelope-Type Systems for Systemic siRNA Delivery.

作者信息

Vhora Imran, Patil Sushilkumar, Amrutiya Jitendra, Misra Ambikanandan

机构信息

Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Kalabhavan, Vadodara -390001, Gujarat, INDIA.

出版信息

Curr Pharm Des. 2015;21(31):4541-55. doi: 10.2174/138161282131151013185850.

Abstract

The 'RNA interference' has emerged as a potential therapeutic strategy owing to its high specificity to silent any malfunctioned gene in diseases with genetic background. Currently intravenous delivery of siRNA has been a preferred way of administration due to high access of blood to the organs where direct delivery is not possible. Among non-viral delivery systems enabling systemic delivery of siRNA, liposomes and lipid envelope systems appear to be promising due to their biocompatibility over other systems. However, these systems are still challenged by toxicity issues, instability in blood, non-specific distribution and low transfection efficiency after intravenous administration. Therefore, to increase the success of lipid based siRNA delivery, it is essential to understand the importance of various factors affecting the efficiency of siRNA delivery. The current review focuses on the formulation of lipid based siRNA formulations, the challenges posed in systemic delivery and various aspects affecting the transfection efficiency of such formulations. The review also focuses on emerging strategies for lipid based siRNA delivery and overviews clinical prospects for better development of siRNA delivery systems in future. Considering the current trends, it seems that liposomes and lipid based envelope systems for systemic delivery of siRNA will translate into extensive clinical application overcoming the associated challenges in near future.

摘要

“RNA干扰”已成为一种潜在的治疗策略,因为它对沉默具有遗传背景疾病中的任何功能异常基因具有高度特异性。目前,由于血液可大量进入无法进行直接递送的器官,静脉内递送小干扰RNA(siRNA)已成为一种首选的给药方式。在能够实现siRNA全身递送的非病毒递送系统中,脂质体和脂质包膜系统因其相对于其他系统的生物相容性而显得很有前景。然而,这些系统仍然受到毒性问题、血液中的不稳定性、非特异性分布以及静脉给药后转染效率低的挑战。因此,为了提高基于脂质的siRNA递送的成功率,了解影响siRNA递送效率的各种因素的重要性至关重要。当前的综述聚焦于基于脂质的siRNA制剂的配方、全身递送中面临的挑战以及影响此类制剂转染效率的各个方面。该综述还关注基于脂质的siRNA递送的新兴策略,并概述未来更好地开发siRNA递送系统的临床前景。考虑到当前的趋势,用于siRNA全身递送的脂质体和基于脂质的包膜系统似乎将在不久的将来克服相关挑战,转化为广泛的临床应用。

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