Hydrophobic blocks of PEG-conjugates play a significant role in the accelerated blood clearance (ABC) phenomenon
Injections of poly(ethylene glycol)-modified liposomes (PEG-liposomes) cause rapid clearance of the second dose of PEG-liposomes. This phenomenon is known as the accelerated blood clearance (ABC) phenomenon. Previous studies have suggested that PEG-specific IgM (anti-PEG IgM) can play a major role i...
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| Veröffentlicht in: | Journal of controlled release 2013-02, Vol.165 (3), p.183-190 |
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| creator | Shiraishi, Kouichi Hamano, Mikiko Ma, Huili Kawano, Kumi Maitani, Yoshie Aoshi, Taiki Ishii, Ken J. Yokoyama, Masayuki |
| description | Injections of poly(ethylene glycol)-modified liposomes (PEG-liposomes) cause rapid clearance of the second dose of PEG-liposomes. This phenomenon is known as the accelerated blood clearance (ABC) phenomenon. Previous studies have suggested that PEG-specific IgM (anti-PEG IgM) can play a major role in the ABC phenomenon. In our previous study, however, a PEG-shell-possessing polymeric micelle with hydrophilic inner core (PEG-P(Lys-DOTA-Gd) micelle) did not induce the ABC phenomenon nor the IgM responses, and exhibited no change in its plasma concentration in PEG-liposome-injected mice. In the present paper, we studied the ABC-phenomenon in more detail by comparing the behaviors between PEG-liposomes, PEG-P(Lys-DOTA-Gd) micelle, and hydrophobic-core-possessing PEG-PBLA micelles. We demonstrated that the PEG-PBLA micelle induced similar IgM responses as observed in PEG-liposome; however, the second dose of PEG-PBLA micelle exhibited no decreases in their plasma concentration, while the second dose of PEG-liposome did exhibit rapid clearances. Furthermore, we did not observe any PEG main chain specific IgM in PEG-liposome injected mice by sandwich ELISA which can measure more specific IgM to the PEG main chain theoretically. These results suggested that the induced IgM recognizes an interface between PEG chain and hydrophobic chain, rather than PEG main chain, and the anti-PEG IgM hypothesis should be re-evaluated.
The IgM binds to PEG-DSPE in a conventional ELISA, but does not bind to PEG-DSPE in a sandwich ELISA. The IgM recognizes an interface between PEG and hydrophobic blocks. [Display omitted] |
| doi_str_mv | 10.1016/j.jconrel.2012.11.016 |
| format | Article |
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The IgM binds to PEG-DSPE in a conventional ELISA, but does not bind to PEG-DSPE in a sandwich ELISA. The IgM recognizes an interface between PEG and hydrophobic blocks. [Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2012.11.016</identifier><identifier>PMID: 23220106</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Accelerated blood clearance (ABC) phenomenon ; Animals ; Blood ; Enzyme-Linked Immunosorbent Assay ; ethylene glycol ; Gadolinium - administration & dosage ; Gadolinium - chemistry ; Gadolinium - pharmacokinetics ; hydrophilicity ; Hydrophilic–hydrophobic interface ; Hydrophobic and Hydrophilic Interactions ; hydrophobicity ; IgM binding ; Immunoglobulin G - blood ; immunoglobulin M ; Immunoglobulin M - blood ; Kidney - metabolism ; Liposomes ; Liver - metabolism ; Male ; Metabolic Clearance Rate ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Micelles ; Poly(ethylene glycol) (PEG) ; Polyethylene Glycols - administration & dosage ; Polyethylene Glycols - chemistry ; Polyethylene Glycols - pharmacokinetics ; Polymeric micelle ; Spleen - metabolism</subject><ispartof>Journal of controlled release, 2013-02, Vol.165 (3), p.183-190</ispartof><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-f8956c9398c497f6eb59e236198d7b6790a74744f99c09faa45045e675d4c0473</citedby><cites>FETCH-LOGICAL-c488t-f8956c9398c497f6eb59e236198d7b6790a74744f99c09faa45045e675d4c0473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2012.11.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23220106$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shiraishi, Kouichi</creatorcontrib><creatorcontrib>Hamano, Mikiko</creatorcontrib><creatorcontrib>Ma, Huili</creatorcontrib><creatorcontrib>Kawano, Kumi</creatorcontrib><creatorcontrib>Maitani, Yoshie</creatorcontrib><creatorcontrib>Aoshi, Taiki</creatorcontrib><creatorcontrib>Ishii, Ken J.</creatorcontrib><creatorcontrib>Yokoyama, Masayuki</creatorcontrib><title>Hydrophobic blocks of PEG-conjugates play a significant role in the accelerated blood clearance (ABC) phenomenon</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Injections of poly(ethylene glycol)-modified liposomes (PEG-liposomes) cause rapid clearance of the second dose of PEG-liposomes. This phenomenon is known as the accelerated blood clearance (ABC) phenomenon. Previous studies have suggested that PEG-specific IgM (anti-PEG IgM) can play a major role in the ABC phenomenon. In our previous study, however, a PEG-shell-possessing polymeric micelle with hydrophilic inner core (PEG-P(Lys-DOTA-Gd) micelle) did not induce the ABC phenomenon nor the IgM responses, and exhibited no change in its plasma concentration in PEG-liposome-injected mice. In the present paper, we studied the ABC-phenomenon in more detail by comparing the behaviors between PEG-liposomes, PEG-P(Lys-DOTA-Gd) micelle, and hydrophobic-core-possessing PEG-PBLA micelles. We demonstrated that the PEG-PBLA micelle induced similar IgM responses as observed in PEG-liposome; however, the second dose of PEG-PBLA micelle exhibited no decreases in their plasma concentration, while the second dose of PEG-liposome did exhibit rapid clearances. Furthermore, we did not observe any PEG main chain specific IgM in PEG-liposome injected mice by sandwich ELISA which can measure more specific IgM to the PEG main chain theoretically. These results suggested that the induced IgM recognizes an interface between PEG chain and hydrophobic chain, rather than PEG main chain, and the anti-PEG IgM hypothesis should be re-evaluated.
The IgM binds to PEG-DSPE in a conventional ELISA, but does not bind to PEG-DSPE in a sandwich ELISA. The IgM recognizes an interface between PEG and hydrophobic blocks. [Display omitted]</description><subject>Accelerated blood clearance (ABC) phenomenon</subject><subject>Animals</subject><subject>Blood</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>ethylene glycol</subject><subject>Gadolinium - administration & dosage</subject><subject>Gadolinium - chemistry</subject><subject>Gadolinium - pharmacokinetics</subject><subject>hydrophilicity</subject><subject>Hydrophilic–hydrophobic interface</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>hydrophobicity</subject><subject>IgM binding</subject><subject>Immunoglobulin G - blood</subject><subject>immunoglobulin M</subject><subject>Immunoglobulin M - blood</subject><subject>Kidney - metabolism</subject><subject>Liposomes</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Metabolic Clearance Rate</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Micelles</subject><subject>Poly(ethylene glycol) (PEG)</subject><subject>Polyethylene Glycols - administration & dosage</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Polyethylene Glycols - pharmacokinetics</subject><subject>Polymeric micelle</subject><subject>Spleen - metabolism</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUuP0zAUhS0EYjoDPwHwclgk2ImfKzRU80AaCSSYteU4161DGgc7Req_x1UL21lYlq6_c3x0D0LvKKkpoeLTUA8uTgnGuiG0qSmty_QFWlEl24ppzV-iVZmoqhVcX6DLnAdCCG-ZfI0umrYpKiJWaH449CnO29gFh7sxul8ZR4-_395XxX7Yb-wCGc-jPWCLc9hMwQdnpwWnOAIOE162gK1zMEIqaH_0iD12I9hkJwf4-ubL-iOetzDFXTnTG_TK2zHD2_N9hZ7ubn-uH6rHb_df1zePlWNKLZVXmgunW60c09IL6LiGphVUq152QmpiJZOMea0d0d5axgnjICTvmSNMtlfo-uQ7p_h7D3kxu5BLzNFOEPfZUE6IlI1S4nm0ka3QmnBeUH5CXYo5J_BmTmFn08FQYo69mMGcezHHXgylpkyL7v35i323g_6_6l8RBfhwAryNxm5SyObpR3kqKamUhKpCfD4RULb2J0Ay2QUoK-5DAreYPoZnQvwFqc2pGg</recordid><startdate>20130210</startdate><enddate>20130210</enddate><creator>Shiraishi, Kouichi</creator><creator>Hamano, Mikiko</creator><creator>Ma, Huili</creator><creator>Kawano, Kumi</creator><creator>Maitani, Yoshie</creator><creator>Aoshi, Taiki</creator><creator>Ishii, Ken J.</creator><creator>Yokoyama, Masayuki</creator><general>Elsevier B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20130210</creationdate><title>Hydrophobic blocks of PEG-conjugates play a significant role in the accelerated blood clearance (ABC) phenomenon</title><author>Shiraishi, Kouichi ; Hamano, Mikiko ; Ma, Huili ; Kawano, Kumi ; Maitani, Yoshie ; Aoshi, Taiki ; Ishii, Ken J. ; Yokoyama, Masayuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-f8956c9398c497f6eb59e236198d7b6790a74744f99c09faa45045e675d4c0473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Accelerated blood clearance (ABC) phenomenon</topic><topic>Animals</topic><topic>Blood</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>ethylene glycol</topic><topic>Gadolinium - administration & dosage</topic><topic>Gadolinium - chemistry</topic><topic>Gadolinium - pharmacokinetics</topic><topic>hydrophilicity</topic><topic>Hydrophilic–hydrophobic interface</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>hydrophobicity</topic><topic>IgM binding</topic><topic>Immunoglobulin G - blood</topic><topic>immunoglobulin M</topic><topic>Immunoglobulin M - blood</topic><topic>Kidney - metabolism</topic><topic>Liposomes</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Metabolic Clearance Rate</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Micelles</topic><topic>Poly(ethylene glycol) (PEG)</topic><topic>Polyethylene Glycols - administration & dosage</topic><topic>Polyethylene Glycols - chemistry</topic><topic>Polyethylene Glycols - pharmacokinetics</topic><topic>Polymeric micelle</topic><topic>Spleen - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shiraishi, Kouichi</creatorcontrib><creatorcontrib>Hamano, Mikiko</creatorcontrib><creatorcontrib>Ma, Huili</creatorcontrib><creatorcontrib>Kawano, Kumi</creatorcontrib><creatorcontrib>Maitani, Yoshie</creatorcontrib><creatorcontrib>Aoshi, Taiki</creatorcontrib><creatorcontrib>Ishii, Ken J.</creatorcontrib><creatorcontrib>Yokoyama, Masayuki</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shiraishi, Kouichi</au><au>Hamano, Mikiko</au><au>Ma, Huili</au><au>Kawano, Kumi</au><au>Maitani, Yoshie</au><au>Aoshi, Taiki</au><au>Ishii, Ken J.</au><au>Yokoyama, Masayuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hydrophobic blocks of PEG-conjugates play a significant role in the accelerated blood clearance (ABC) phenomenon</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2013-02-10</date><risdate>2013</risdate><volume>165</volume><issue>3</issue><spage>183</spage><epage>190</epage><pages>183-190</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Injections of poly(ethylene glycol)-modified liposomes (PEG-liposomes) cause rapid clearance of the second dose of PEG-liposomes. This phenomenon is known as the accelerated blood clearance (ABC) phenomenon. Previous studies have suggested that PEG-specific IgM (anti-PEG IgM) can play a major role in the ABC phenomenon. In our previous study, however, a PEG-shell-possessing polymeric micelle with hydrophilic inner core (PEG-P(Lys-DOTA-Gd) micelle) did not induce the ABC phenomenon nor the IgM responses, and exhibited no change in its plasma concentration in PEG-liposome-injected mice. In the present paper, we studied the ABC-phenomenon in more detail by comparing the behaviors between PEG-liposomes, PEG-P(Lys-DOTA-Gd) micelle, and hydrophobic-core-possessing PEG-PBLA micelles. We demonstrated that the PEG-PBLA micelle induced similar IgM responses as observed in PEG-liposome; however, the second dose of PEG-PBLA micelle exhibited no decreases in their plasma concentration, while the second dose of PEG-liposome did exhibit rapid clearances. Furthermore, we did not observe any PEG main chain specific IgM in PEG-liposome injected mice by sandwich ELISA which can measure more specific IgM to the PEG main chain theoretically. These results suggested that the induced IgM recognizes an interface between PEG chain and hydrophobic chain, rather than PEG main chain, and the anti-PEG IgM hypothesis should be re-evaluated.
The IgM binds to PEG-DSPE in a conventional ELISA, but does not bind to PEG-DSPE in a sandwich ELISA. The IgM recognizes an interface between PEG and hydrophobic blocks. [Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>23220106</pmid><doi>10.1016/j.jconrel.2012.11.016</doi><tpages>8</tpages></addata></record> |
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| subjects | Accelerated blood clearance (ABC) phenomenon Animals Blood Enzyme-Linked Immunosorbent Assay ethylene glycol Gadolinium - administration & dosage Gadolinium - chemistry Gadolinium - pharmacokinetics hydrophilicity Hydrophilic–hydrophobic interface Hydrophobic and Hydrophilic Interactions hydrophobicity IgM binding Immunoglobulin G - blood immunoglobulin M Immunoglobulin M - blood Kidney - metabolism Liposomes Liver - metabolism Male Metabolic Clearance Rate Mice Mice, Inbred BALB C Mice, Inbred C57BL Micelles Poly(ethylene glycol) (PEG) Polyethylene Glycols - administration & dosage Polyethylene Glycols - chemistry Polyethylene Glycols - pharmacokinetics Polymeric micelle Spleen - metabolism |
| title | Hydrophobic blocks of PEG-conjugates play a significant role in the accelerated blood clearance (ABC) phenomenon |
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