Using drug-excipient interactions for siRNA delivery()

Bruno, Katharina

SiRNA is the trigger of RNA interference, a mechanism discovered in the late 1990s. To release the therapeutic potential of this versatile but large and fragile molecule, excipients are used which either interact by electrostatic interaction, passively encapsulate siRNA or are covalently attached to enable specific and safe delivery of the drug substance. Controlling the delicate balance between protective complexation and release of siRNA at the right point and time is done by understanding excipients–siRNA interactions. These can be lipids, polymers such as PEI, PLGA, Chitosans, Cyclodextrins, as well as aptamers and peptides. This review describes the mechanisms of interaction of the most commonly used siRNA delivery vehicles, and looks at the results of their clinical and preclinical studies.