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.