| T cell-independent B cell response is responsible for ABC phenomenon induced by repeated injection of PEGylated liposomes. | |
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MedLine Citation:
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PMID: 20227473 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Repeated injection of polyethyleneglycol-modified (PEGylated) liposomes causes a rapid clearance of them from the bloodstream, this phenomenon is called accelerated blood clearance (ABC). In the present study, we focused on the immune system responsible for the ABC phenomenon. PEGylated liposomes were preadministered to BALB/c mice and [(3)H]-labeled ones were then administered to them 3 days after the preadministration. Consistent with our previous results, the preadministration with PEGylated liposomes triggered the rapid clearance of [(3)H]-labeled PEGylated liposomes from the bloodstream, but that with PEGylated liposomes encapsulating doxorubicin (Dox) did not. In addition, we found that the ABC phenomenon was observed when a mixture of free Dox and PEGylated liposomes was preadministered. These data indicate that immune cells responsible for the ABC phenomenon might be selectively damaged by the Dox encapsulated in PEGylated liposomes. The ABC phenomenon was also observed in BALB/c nu/nu mice, but not in BALB/c SCID mice. The amount of anti-PEG IgM antibody induced by the stimulation with the PEGylated liposomes was significantly increased in the BALB/c nu/nu mice, but not in the BALB/c SCID ones. These data indicate that a T cell-independent B cell response would play a significant role in the ABC phenomenon. Furthermore, the present study suggests that PEGylated liposomes might be recognized by B cells as a thymus-independent type 2 (TI-2) antigen. The present study provides important information for the future development of liposomal medicines. |
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Authors:
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Hiroyuki Koide; Tomohiro Asai; Kentaro Hatanaka; Shuji Akai; Takayuki Ishii; Eriya Kenjo; Tatsuhiro Ishida; Hiroshi Kiwada; Hideo Tsukada; Naoto Oku |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-21 |
Journal Detail:
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Title: International journal of pharmaceutics Volume: 392 ISSN: 1873-3476 ISO Abbreviation: Int J Pharm Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-14 Completed Date: 2010-09-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 218-23 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Medical Biochemistry and Global COE Program, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, T-Independent / immunology* B-Lymphocytes / drug effects*, immunology Dose-Response Relationship, Drug Doxorubicin / administration & dosage, pharmacokinetics, pharmacology* Immunoglobulin M / immunology* Injections, Intravenous Liposomes / administration & dosage, blood, immunology* Male Metabolic Clearance Rate Mice Mice, Inbred BALB C Mice, SCID Polyethylene Glycols / administration & dosage, pharmacokinetics, pharmacology* T-Lymphocytes / drug effects, immunology Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/Antigens, T-Independent; 0/Immunoglobulin M; 0/Liposomes; 0/Polyethylene Glycols; 23214-92-8/Doxorubicin |
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