Understanding the correlation between in vitro and in vivo immunotoxicity tests for nanomedicines

被引:209
作者
Dobrovolskaia, Marina A. [1 ]
McNeil, Scott E. [1 ]
机构
[1] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA
基金
美国国家卫生研究院;
关键词
Nanoparticles; Thrombosis; Disseminated intravascular coagulation; Procoagulant activity; Coagulopathy; Hemolysis; Complement activation; Cytokines; Anaphylaxis; Phagocytosis; CFU-GM ASSAY; HUMAN WHOLE-BLOOD; COMPLEMENT ACTIVATION; IMMUNE-SYSTEM; PROCOAGULANT ACTIVITY; RISK-ASSESSMENT; EXTENDED HISTOPATHOLOGY; PLATELET-AGGREGATION; SCAVENGER RECEPTOR; THROMBUS FORMATION;
D O I
10.1016/j.jconrel.2013.05.025
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Preclinical characterization of novel nanotechnology-based formulations is often challenged by physicochemical characteristics, sterility/sterilization issues, safety and efficacy. Such challenges are not unique to nanomedicine, as they are common in the development of small and macromolecular drugs. However, due to the lack of a general consensus on critical characterization parameters, a shortage of harmonized protocols to support testing, and the vast variety of engineered nanomaterials, the translation of nanomedicines into clinic is particularly complex. Understanding the immune compatibility of nanoformulations has been identified as one of the important factors in (pre) clinical development and requires reliable in vitro and in vivo immunotoxicity tests. The generally low sensitivity of standard in vivo toxicity tests to immunotoxicities, inter-species variability in the structure and function of the immune system, high costs and relatively low throughput of in vivo tests, and ethical concerns about animal use underscore the need for trustworthy in vitro assays. Here, we consider the correlation (or lack thereof) between in vitro and in vivo immunotoxicity tests as a mean to identify useful in vitro assays. We review literature examples and case studies from the experience of the NCI Nanotechnology Characterization Lab, and highlight assays where predictability has been demonstrated for a variety of nanomaterials and assays with high potential for predictability in vivo. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:456 / 466
页数:11
相关论文
共 114 条
[41]   Pharmacokinetics of a tumor necrosis factor-α phosphorothioate 2′-O-(2-methoxyethyl) modified antisense oligonucleotide:: Comparison across species [J].
Geary, RS ;
Yu, RZ ;
Watanabe, T ;
Henry, SP ;
Hardee, GE ;
Chappell, A ;
Matson, J ;
Sasmor, H ;
Cummins, L ;
Levin, AA .
DRUG METABOLISM AND DISPOSITION, 2003, 31 (11) :1419-1428
[42]   Update on Macrophage Clearance of Inhaled Micro- and Nanoparticles [J].
Geiser, Marianne .
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, 2010, 23 (04) :207-217
[43]   The accuracy of extended histopathology to detect immunotoxic chemicals [J].
Germolec, DR ;
Kashon, M ;
Nyska, A ;
Kuper, CF ;
Portier, C ;
Kommineni, C ;
Johnson, KA ;
Luster, MI .
TOXICOLOGICAL SCIENCES, 2004, 82 (02) :504-514
[44]   Extended histopathology in immunotoxicity testing: Interlaboratory validation studies [J].
Germolec, DR ;
Nyska, A ;
Kashon, M ;
Kuper, CF ;
Portier, C ;
Kommineni, C ;
Johnson, KA ;
Luster, MI .
TOXICOLOGICAL SCIENCES, 2004, 78 (01) :107-115
[45]   Acute Toxicity and Prothrombotic Effects of Quantum Dots: Impact of Surface Charge [J].
Geys, Jorina ;
Nemmar, Abderrahim ;
Verbeken, Erik ;
Smolders, Erik ;
Ratoi, Monica ;
Hoylaerts, Marc F. ;
Nemery, Benoit ;
Hoet, Peter H. M. .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2008, 116 (12) :1607-1613
[46]   INCREASED BONE-MARROW TOXICITY OF DOXORUBICIN BOUND TO NANOPARTICLES [J].
GIBAUD, S ;
ANDREUX, JP ;
WEINGARTEN, C ;
RENARD, M ;
COUVREUR, P .
EUROPEAN JOURNAL OF CANCER, 1994, 30A (06) :820-826
[47]   Use of CFU-GM assay for prediction of human maximum tolerated dose of a new antitumoral drug:: Yondelis™ (ET-743) [J].
Gómez, SG ;
Bueren, JA ;
Faircloth, G ;
Albella, B .
TOXICOLOGY IN VITRO, 2003, 17 (5-6) :671-674
[48]   Size and surface charge significantly influence the toxicity of silica and dendritic nanoparticles [J].
Greish, Khaled ;
Thiagarajan, Giridhar ;
Herd, Heather ;
Price, Robert ;
Bauer, Hillevi ;
Hubbard, Dallin ;
Burckle, Alexander ;
Sadekar, Shraddha ;
Yu, Tian ;
Anwar, Arnida ;
Ray, Abhijit ;
Ghandehari, Hamidreza .
NANOTOXICOLOGY, 2012, 6 (07) :713-723
[49]  
Hartung T., 2011, REV NANOMED NANOBIOT
[50]   Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide [J].
Henry, SP ;
Beattie, G ;
Yeh, G ;
Chappel, A ;
Giclas, P ;
Mortari, A ;
Jagels, MA ;
Kornbrust, DJ ;
Levin, AA .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2002, 2 (12) :1657-1666