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

Pharmaceutics

Masako Ichihara²  Taro Shimizu²  Ami Imoto²  Yuki Hashiguchi²  Yumi Uehara²  Tatsuhiro Ishida¹ 

[1] id="af1-pharmaceutics-03-00001">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, Jap

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

DOI  :  10.3390/pharmaceutics3010001

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland.