Abstract:
PURPOSE:To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC) and intravenous (IV) administration in mice and measure their propensity to stimulate an early immune response. METHODS:A human mAb (IgG1) was fluorescently labeled, aggregated by agitation stress and injected in SKH1 mice through SC and IV routes. The biodistribution of monomeric and aggregated formulations was monitored over 47 days by fluorescence imaging and the early immune response was measured by quantifying the level of relevant cytokines in serum using a Bio-plex assay. RESULTS:The aggregates remained at the SC injection site for a longer time than monomers but after entry into the systemic circulation disappeared faster than monomers. Upon IV administration, both monomers and aggregates spread rapidly throughout the circulation, and a strong accumulation in the liver was observed for both species. Subsequent removal from the circulation was faster for aggregates than monomers. No accumulation in lymph nodes was observed after SC or IV administration. Administration of monomers and aggregates induced similar cytokine levels, but SC injection resulted in higher cytokine levels than IV administration. CONCLUSION:These results show differences in biodistribution and residence time between IgG1 aggregates and monomers. The long residence time of aggregates at the SC injection site, in conjunction with elevated cytokine levels, may contribute to an enhanced immunogenicity risk of SC injected aggregates compared to that of monomers.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Filipe V,Que I,Carpenter JF,Löwik C,Jiskoot Wdoi
10.1007/s11095-013-1154-9subject
Has Abstractpub_date
2014-01-01 00:00:00pages
216-27issue
1eissn
0724-8741issn
1573-904Xjournal_volume
31pub_type
杂志文章abstract::Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. T...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015852732512
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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abstract:PURPOSE:Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of pacli...
journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2003-11-01 00:00:00
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
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pub_type: 杂志文章,已发布勘误
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1992-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1997-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018967401000
更新日期:1994-12-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016028707130
更新日期:1996-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:2005-08-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1995-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015840320410
更新日期:1991-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012108118670
更新日期:1997-07-01 00:00:00