Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes

Els T. M. Dams, Peter Laverman, Wim J. G. Oyen, Gert Storm, Gerrit L. Scherphof, Jos W. M. van der Meer, Frans H. M. Corstens and Otto C. Boerman
Journal of Pharmacology and Experimental Therapeutics March 2000, 292 (3) 1071-1079;
Els T. M. Dams
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Laverman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wim J. G. Oyen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gert Storm
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerrit L. Scherphof
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jos W. M. van der Meer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frans H. M. Corstens
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Otto C. Boerman
  • 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

Abstract

Sterically stabilized liposomes are considered promising carriers of therapeutic agents because they can facilitate controlled release of the drugs, thereby reducing drug-related toxicity and/or targeted delivery of drugs. Herein, we studied the pharmacokinetics and biodistribution of repeated injections of radiolabeled polyethyleneglycol (PEG) liposomes. Weekly injections of99mTc-PEG liposomes dramatically influenced the circulatory half-life in rats. Biodistribution 4 h after the second dose showed a significantly reduced blood content (from 52.6 ± 3.7 to 0.6 ± 0.1% injected dose (ID), P < .01) accompanied by a highly increased uptake in the liver (from 8.1 ± 0.8 to 46.2 ± 9.8%ID, P < .01) and in the spleen (from 2.2 ± 0.2 to 5.3 ± 0.7%ID,P < .01). At subsequent injections the effect was less pronounced: after the fourth dose, the pharmacokinetics of the radiolabel had almost returned to normal. The same phenomenon was observed in a rhesus monkey, but not in mice. The enhanced blood clearance of the PEG liposomes also was observed in rats after transfusion of serum from rats that had received PEG liposomes 1 week earlier, indicating that the enhanced blood clearance was caused by a soluble serum factor. This serum factor was a heat-labile molecule that coeluted on a size exclusion column with a 150-kDa protein. In summary, i.v. administration of sterically stabilized PEG liposomes significantly altered the pharmacokinetic behavior of subsequently injected PEG liposomes in a time- and frequency-dependent manner. The observed phenomenon may have important implications for the repeated administration of sterically stabilized liposomes for targeted drug delivery.

Footnotes

  • Send reprint requests to: Otto C. Boerman, Ph.D., Department of Nuclear Medicine, University Medical Centre St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail:O.Boerman{at}nugen.azn.nl

  • ↵1 This study was supported by Grant no. NGN 55.3665 from the Technology Foundation (Technologiestichting STW), the Netherlands.

  • Abbreviations:
    DOX
    doxorubicin
    MPS
    mononuclear phagocyte system
    PEG
    polyethyleneglycol
    PHEPC
    partially hydrogenated egg-phosphatidylcholine
    DSPE
    distearoylphosphatidyl-ethanolamine
    HYNIC
    N-hydroxysuccinimidyl hydrazino nicotinate hydrochloride
    ID
    injected dose
    ROI
    region of interest
    • Received August 13, 1999.
    • Accepted November 19, 1999.
  • 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: 292 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 3
1 Mar 2000
  • Table of Contents
  • About the Cover
  • Index by author
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.
Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes
(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 ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes

Els T. M. Dams, Peter Laverman, Wim J. G. Oyen, Gert Storm, Gerrit L. Scherphof, Jos W. M. van der Meer, Frans H. M. Corstens and Otto C. Boerman
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1071-1079;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Accelerated Blood Clearance and Altered Biodistribution of Repeated Injections of Sterically Stabilized Liposomes

Els T. M. Dams, Peter Laverman, Wim J. G. Oyen, Gert Storm, Gerrit L. Scherphof, Jos W. M. van der Meer, Frans H. M. Corstens and Otto C. Boerman
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1071-1079;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Transport Is Not Rate-Limiting in Morphine Glucuronidation in the Single-Pass Perfused Rat Liver Preparation
  • Enhanced Hepatic Uptake and Bioactivity of Type α1(I) Collagen Gene Promoter-Specific Triplex-Forming Oligonucleotides after Conjugation with Cholesterol
  • Characterization of P-glycoprotein Inhibition by Major Cannabinoids from Marijuana
Show more ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics