Delivery of large biopharmaceuticals from cardiovascular stents: a review

This review focuses on new and emerging large-molecule bioactive agents delivered from stent surfaces in drug-eluting stents (DESs) to inhibit vascular restenosis in the context of interventional cardiology. New therapeutic agents representing proteins, nucleic acids (small interfering RNAs and large DNA plasmids), viral delivery vectors, and even engineered cell therapies require specific delivery designs distinct from traditional smaller-molecule approaches on DESs. While small molecules are currently the clinical standard for coronary stenting, extension of the DESs to other lesion types, peripheral vasculature, and nonvasculature therapies will seek to deliver an increasingly sophisticated armada of drug types. This review describes many of the larger-molecule and biopharmaceutical approaches reported recently for stent-based delivery with the challenges associated with formulating and delivering these drug classes compared to the current small-molecule drugs. It also includes perspectives on possible future applications that may improve safety and efficacy and facilitate diversification of the DESs to other clinical applications.