Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anticancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines

Lin Ao, Derek Reichel, Di Hu, Hyunyoung Jeong, Kyung Bo Kim, Younsoo Bae and Wooin Lee
Journal of Pharmacology and Experimental Therapeutics November 2015, 355 (2) 168-173; DOI: https://doi.org/10.1124/jpet.115.226993
Lin Ao
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derek Reichel
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Di Hu
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyunyoung Jeong
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyung Bo Kim
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Younsoo Bae
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wooin Lee
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky (L.A., D.R., K.B.K., Y.B.); Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois (D.H., H.J.); and College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea (W.L.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Visual Overview

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

Carfilzomib (CFZ) is a second-generation proteasome inhibitor drug approved for the treatment of multiple myeloma. Contrary to its excellent antimyeloma activity, CFZ has shown only limited efficacy in patients with solid malignancies. This lack of efficacy has been attributed in part to rapid degradation of CFZ in the body, possibly hindering the ability of CFZ to access the proteasome target in solid tumors. We hypothesized that polymer micelles, a currently Food and Drug Administration–approved nanoparticle drug delivery formulation, may protect CFZ from metabolic degradation and thus expand the clinical utility of the drug as an anticancer agent. To test our hypothesis, we prepared CFZ-entrapped polymer micelle particles with various compositions and drug release profiles and examined the extent of the CFZ metabolism in vitro using mouse liver homogenates. We also assessed the cytotoxic activities of the CFZ-entrapped micelle formulations in human cancer cell lines derived from B lymphocytes (RPMI-8226) and the lung (H460). Our data indicated that polymer micelle-based formulations can improve metabolic stability and cytotoxic effects of CFZ compared with free CFZ in human cancer cell lines tested. Taken together, these results suggest that polymer micelles may have potential as a delivery system for CFZ with an extended therapeutic utility for nonhematologic malignancies in the future.

Footnotes

    • Received June 25, 2015.
    • Accepted August 25, 2015.
  • This work was supported by the National Institutes of Health [Grants R01-CA128903 and R15-CA156601]; American Foundation for Pharmaceutical Education Pre-Doctoral Fellowship; and Basic Science Research Program, National Research Foundation of Korea, Ministry of Science, ICT and Future Planning [NRF-2014R1A1A3050645].

  • dx.doi.org/10.1124/jpet.115.226993.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 355 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 355, Issue 2
1 Nov 2015
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Polymer Micelle Formulations of Proteasome Inhibitor Carfilzomib for Improved Metabolic Stability and Anticancer Efficacy in Human Multiple Myeloma and Lung Cancer Cell Lines
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Micelle Formulation of Carfilzomib for Improved Anticancer Efficacy

Lin Ao, Derek Reichel, Di Hu, Hyunyoung Jeong, Kyung Bo Kim, Younsoo Bae and Wooin Lee
Journal of Pharmacology and Experimental Therapeutics November 1, 2015, 355 (2) 168-173; DOI: https://doi.org/10.1124/jpet.115.226993

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Micelle Formulation of Carfilzomib for Improved Anticancer Efficacy

Lin Ao, Derek Reichel, Di Hu, Hyunyoung Jeong, Kyung Bo Kim, Younsoo Bae and Wooin Lee
Journal of Pharmacology and Experimental Therapeutics November 1, 2015, 355 (2) 168-173; DOI: https://doi.org/10.1124/jpet.115.226993
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Visual Overview
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Targeting LGR5-Positive Cells in Ovarian Cancer
  • Ocular Palonosetron for Prevention of Nausea and Vomiting
  • PTP4A3 and Ovarian Cancer
Show more Chemotherapy, Antibiotics, and Gene Therapy

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics