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.
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