Pharmacokinetic aspects of the clinically used proteasome inhibitor drugs and efforts toward nanoparticulate delivery systems

Abstract

Background Proteasome inhibitor drugs have provided a major breakthrough in the treatment of multiple myeloma and other hematological malignancies. Currently, there are three clinically used proteasome inhibitor drugs, namely bortezomib, carfilzomib, and ixazomib. Fueled by the remarkable successes of these drugs, additional drug candidates are actively pursued by targeting the proteasome and other components in the ubiquitin-proteasome pathways. Efforts are ongoing to overcome the drawbacks of the existing proteasome inhibitor drugs, optimize their pharmacokinetic aspects, and expand their clinical utility beyond the current indications, in particular for solid cancer therapy. Over the several decades, a variety of nanoparticulate delivery systems have been designed and applied to cancer therapy with a goal of improving the efficacy and safety. Area covered This review summarizes the pharmacokinetic aspects of the clinically used proteasome inhibitor drugs and the notable findings from the recent reports on the novel nanoparticulate delivery systems of bortezomib and carfilzomib. Expert opinion With the help of novel nanoparticulate delivery systems, the therapeutic utility of the proteasome inhibitor drugs is likely to expand to various types of cancer and other pathological conditions including neurodegenerative and inflammatory diseases.