• Submit to Pharmaceutics Login Register
• MDPI
• Journals A-Z
• For Authors
• For Editors
• About
• Open Access Policy

• Abstract
• Full-Text PDF [173 KB]
• Full-Text XML
• Article Versions Notes

• Article Statistics
• Google Scholar
• Order Reprints

• Cite this article
• Export to BibTeX
• Export to EndNote

• [+] on DOAJ
• Ichihara, M
• Shimizu, T
• Imoto, A
• Hashiguchi, Y
• Uehara, Y
• Ishida, T
• Kiwada, H
• [+] on Google Scholar
• Ichihara, M
• Shimizu, T
• Imoto, A
• Hashiguchi, Y
• Uehara, Y
• Ishida, T
• Kiwada, H
• [+] on PubMed
• Ichihara, M
• Shimizu, T
• Imoto, A
• Hashiguchi, Y
• Uehara, Y
• Ishida, T
• Kiwada, H

•  CiteULike
•  Facebook
•  Mendeley
•  Twitter

This article is

• freely available
• re-usable

Pharmaceutics 2011, 3(1), 1-11; doi:10.3390/pharmaceutics3010001

Article

Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats

Masako Ichihara, Taro Shimizu, Ami Imoto, Yuki Hashiguchi, Yumi Uehara, Tatsuhiro Ishida*  and Hiroshi Kiwada

Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Science, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505, Japan

* Author to whom correspondence should be addressed.

Received: 24 November 2010; in revised form: 15 December 2010 / Accepted: 24 December 2010 / Published: 27 December 2010

(This article belongs to the Special Issue Nanotechnology in Drug Delivery)

Download PDF Full-Text [173 KB, uploaded 27 December 2010 14:28 CET]

Abstract: We have reported that PEGylated liposomes lose their long-circulating properties when they are administered repeatedly at certain intervals to the same animal. This unexpected phenomenon is referred to as the accelerated blood clearance (ABC) phenomenon. We recently showed that the ABC phenomenon is triggered via the abundant secretion of anti-PEG IgM in response to the first dose of PEGylated liposomes. However, the details of the underlying mechanism for the induction of anti-PEG IgM production are yet to be elucidated. The present study demonstrated that the spleen is a major organ involved in the secretion of anti-PEG IgM in mice and rats. Anti-PEG IgM production was detected in nude, T-cell deficient mice, but not in SCID mice with B- and T-cell deficiencies. These observations indicate that splenic B-cells secret anti-PEG IgM without help from T-cells. Sequential injections of PEGylated liposomes into the same mice did not promote isotype switching from IgM to IgG. Accordingly, PEGylated liposomes may function as a type-2, T-cell-independent antigen (TI-2 antigen) during anti-PEG IgM production. Although the underlying mechanism that causes an anti-PEG IgM response against PEGylated liposomes is not yet clear, our findings give implications in revealing the anti-PEG IgM response against PEGylated liposome.

Keywords: Polyethyleneglycol (PEG); PEGylated liposome; Anti-PEG IgM; Accelerated blood clearance (ABC) phenomenon; spleen

Article Statistics

Cite This Article