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Keywords = Accelerated blood clearance (ABC) phenomenon

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13 pages, 5490 KiB  
Article
Polysialic Acid Modified Liposomes for Improving Pharmacokinetics and Overcoming Accelerated Blood Clearance Phenomenon
by Xi Han, Ting Zhang, Mengyang Liu, Yanzhi Song, Xinrong Liu and Yihui Deng
Coatings 2020, 10(9), 834; https://doi.org/10.3390/coatings10090834 - 28 Aug 2020
Cited by 9 | Viewed by 3020
Abstract
Poly (ethylene glycol) (PEG) modified nanocarriers are being used widely in the drug delivery system (DDS). However, the “accelerated blood clearance (ABC) phenomenon” was induced upon repeated administration of PEG-modified liposomes, resulting in reduced blood circulation time, and increased accumulation in liver and [...] Read more.
Poly (ethylene glycol) (PEG) modified nanocarriers are being used widely in the drug delivery system (DDS). However, the “accelerated blood clearance (ABC) phenomenon” was induced upon repeated administration of PEG-modified liposomes, resulting in reduced blood circulation time, and increased accumulation in liver and spleen. To avoid the unexpected phenomenon, polysialic acid (PSA) was selected to modify liposomes. PSA is a natural, highly hydrophilic polysaccharide polymer for which no receptors exists in the body. It is non-immunogenic, biodegradable and endows the conjugated bioactive macromolecule and drugs with increased circulation time in vivo. In the present study, the in vivo evaluation showed that PSA modified liposomes (PSA-Lip) afford extended blood circulation in wistar rats and beagle dogs. Moreover, the ABC phenomenon did not occur and the IgM antibody was not induced after repeated injections of PSA-Lip. These results strongly suggest that PSA modification represents a promising strategy to afford good stealth of the liposomes without evoking the ABC phenomenon. Full article
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11 pages, 173 KiB  
Article
Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats
by Masako Ichihara, Taro Shimizu, Ami Imoto, Yuki Hashiguchi, Yumi Uehara, Tatsuhiro Ishida and Hiroshi Kiwada
Pharmaceutics 2011, 3(1), 1-11; https://doi.org/10.3390/pharmaceutics3010001 - 27 Dec 2010
Cited by 132 | Viewed by 11978
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Nanotechnology in Drug Delivery)
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