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Receptor-targeted drug delivery has been extensively explored for active targeting. However, the scarce clinical applications of such delivery systems highlight the implicit hurdles in development of such systems. These hurdles begin with lack of knowledge of differential expression of receptors, their accessibility and identification of newer receptors. Similarly, ligand-specific challenges range from proper choice of ligand and conjugation chemistry, to release of drug/delivery system from ligand. Finally, nanocarrier systems, which offer improved loading, biocompatibility and reduced premature degradation, also face multiple challenges. This review focuses on understanding these challenges, and means to overcome such challenges to develop efficient, targeted drug-delivery systems.

RNA interference (RNAi) is a wondrous phenomenon that silences the expression of targeted genes via distinct messenger RNA degradation pathways. It has the potential as a therapeutic agent for variety of diseases, including viral infections, cancer, and immune diseases. RNAi mainly conducts gene regulation by 3 ways: microRNA, short hairpin RNA, and small interfering RNA. However, in vivo delivery of RNAi therapeutics is restricted because of charge density, molecular weight, and instability in the presence of nucleases. Furthermore, intracellular accumulation and endosomal escape have remained significant barriers in the delivery of these macromolecules. Many viral and nonviral delivery vectors have been thoroughly investigated to overcome these barriers. Researchers have found applications for RNAi in a variety of diseases and, hence, various delivery systems have been explored to satisfy the need. Both local and systemic strategies have been utilized to elicit RNAi's effect and each carries its own therapeutic implications with varying margins of safety. This review is an effort to describe the types of RNAi and their application in a variety of diseases using both local and systemic delivery approaches. It is sure that advancement in this direction will evolve a new landscape for treating a range of diseases.