期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 12, 期 7, 页码 2007-2017出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2016.05.019
关键词
Nanoparticles; PLD; Gulp1; Pharmacokinetics; Pharmacogenetics
资金
- University Cancer Research Funding (UCRF) Grant from the UNC Lineberger Comprehensive Cancer Center
- Carolina Center for Cancer Nanotechnology Excellence (CCCNE) from the NCI [1U54 CA151652]
Nanoparticles ( NP) including liposomes are cleared by phagocytes of the mononuclear phagocyte system. High inter-patient variability in pharmacokinetics of PEGylated liposomal doxorubicin ( PLD) has been reported. We hypothesized that genetic factors may be associated with the variable disposition of PLD. We evaluated plasma and tissue disposition of doxorubicin after administration of PLD at 6 mg/kg IV x1 via tail vein in 23 different male inbred mouse strains. An approximately 13-fold difference in plasma clearance of PLD was observed among inbred strains. We identified a correlation between strain-specific differences in PLD clearance and genetic variation within a genomic region encoding GULP1 ( PTB domain containing engulfment adapter 1) protein using haplotype associated mapping and the efficient mixed-model association algorithms. Our results also show that Gulp1 expression in adipose tissue was associated with PLD disposition in plasma. Our findings suggest that genetic variants may be associated with inter-individual pharmacokinetic differences in NP clearance. (C) 2016 Elsevier Inc. All rights reserved.
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