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

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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.

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Acknowledgements

This work was financially supported in part by Creative-Pioneering Researchers Program through Seoul National University (to W.L.), the National Institutes of Health NCI (R01 CA232419 to Y.Y.) and Trask Innovation Fund (to Y.Y.).

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Authors and Affiliations

  1. Purdue University, West Lafayette, IN, USA

    Seungbin Kwon

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA

    Kyung Bo Kim

  3. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA

    Yoon Yeo

  4. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea

    Wooin Lee

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  1. Seungbin Kwon
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  2. Kyung Bo Kim
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  3. Yoon Yeo
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Correspondence to Wooin Lee.

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Kwon, S., Kim, K.B., Yeo, Y. et al. Pharmacokinetic aspects of the clinically used proteasome inhibitor drugs and efforts toward nanoparticulate delivery systems. J. Pharm. Investig. 51, 483–502 (2021). https://doi.org/10.1007/s40005-021-00532-0

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