Subcutaneous drug delivery from nanoscale systems

Various types of nanoscale drug delivery systems (DDSs) have been developed for therapeutic and/or diagnostic applications. However, most systems have been designed for intravenous or intramuscular delivery, which may have drawbacks such as pain during injection, the inability for self-administration and the requirement for hospitalization, causing patient discomfort and high treatment costs. The subcutaneous route of administration is an attractive approach to circumvent many of these drawbacks. However, the subcutaneous route remains underexplored and is not yet used to its full potential. In this Review, we present key advances in the design of nanoscale DDSs (polymer–drug conjugates, liposomes, nanoparticles, micelles) for subcutaneous delivery. Additionally, we discuss nanoscale DDS-loaded hydrogels to create drug depots after subcutaneous administration, and outline relevant predictive in vitro, ex vivo, in silico and in vivo preclinical models for subcutaneous delivery. Finally, we highlight subcutaneous nanoscale DDSs in clinical trials and on the market and outline translational opportunities.