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

Seungbin Kwon, Kyung Bo Kim, Yoon Yeo, Wooin Lee

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)483-502
Number of pages20
JournalJournal of Pharmaceutical Investigation
Volume51
Issue number4
DOIs
StatePublished - Jul 2021

Bibliographical note

Funding Information:
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.).

Publisher Copyright:
© 2021, The Korean Society of Pharmaceutical Sciences and Technology.

Keywords

  • Bortezomib
  • Carfilzomib
  • Nanoparticulate drug delivery
  • Pharmacokinetics
  • Proteasome inhibitors

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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