LAL test and RPT for endotoxin detection of CPT-11/DSPE-mPEG2000 nanoformulation: What if traditional methods are not applicable?

Yanan Jin; Juanjuan Jia; Chan Li; Jianqi Xue; Jiabei Sun; Kaiyuan Wang; Yaling Gan; Jing Xu; Yaqin Shi; Xingjie Liang

Asian Journal of Pharmaceutical Sciences (May 2018)

LAL test and RPT for endotoxin detection of CPT-11/DSPE-mPEG2000 nanoformulation: What if traditional methods are not applicable?

Yanan Jin,
Juanjuan Jia,
Chan Li,
Jianqi Xue,
Jiabei Sun,
Kaiyuan Wang,
Yaling Gan,
Jing Xu,
Yaqin Shi,
Xingjie Liang

Affiliations

Yanan Jin: College of Chemistry & Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, China
Juanjuan Jia: National Institutes for Food and Drug Control, No. 5, Huatuo Rd., Daxing District, Beijing 102629, China
Chan Li: Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, No. 11, First North Road Zhongguancun, Beijing 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China
Jianqi Xue: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, China
Jiabei Sun: National Institutes for Food and Drug Control, No. 5, Huatuo Rd., Daxing District, Beijing 102629, China
Kaiyuan Wang: Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, No. 11, First North Road Zhongguancun, Beijing 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China
Yaling Gan: Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, No. 11, First North Road Zhongguancun, Beijing 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China
Jing Xu: Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, No. 11, First North Road Zhongguancun, Beijing 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China; Corresponding author. National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China. Tel.: +86 10 82545530.
Yaqin Shi: National Institutes for Food and Drug Control, No. 5, Huatuo Rd., Daxing District, Beijing 102629, China; Corresponding author. National Institutes for Food and Drug Control, No. 5, Huatuo Rd., Daxing District, Beijing 102629, China. Tel.: +86 10 53851506.
Xingjie Liang: College of Chemistry & Environmental Science, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, China; Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Center for Excellence in Nanoscience, No. 11, First North Road Zhongguancun, Beijing 100190, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author. National Center for Nanoscience and Technology of China, No. 11, First North Road Zhongguancun, Beijing 100190, China. Tel.: +86 10 82545569.

Journal volume & issue: Vol. 13, no. 3
pp. 289 – 296

Abstract

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Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride (CPT-11) and an amphiphilic molecule DSPE-mPEG2000 can interfere with the limulus amebocyte lysate assay (LAL). Furthermore, the rabbit pyrogen test (RPT) results indicated that at a relatively high dosage, the drug irinotecan hydrochloride can induce a hypothermia effect which may render the RPT results ambiguous in determination of the safety of the drug formulation.Our findings demonstrate limitations of endotoxin detection in micellar drugs, and call for the necessity of developing reliable endotoxin detection methods that can overcome the interference of nanomaterials in order to better ensure the drug safety of patients in future pharmaceutical drug development. Keywords: Irinotecan hydrochloride, Endotoxin detection, Micelle, DSPE-mPEG2000, Limulus amebocyte lysate assay, Rabbit pyrogen test

Published in Asian Journal of Pharmaceutical Sciences

ISSN: 1818-0876 (Print)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/asian-journal-of-pharmaceutical-sciences/

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