標題: Development of an Anti-Methoxy Poly(ethylene glycol) (alpha-mPEG) Cell-Based Capture System to Measure mPEG and mPEGylated Molecules
作者: Chuang, Kuo-Hsiang
Kao, Chien-Han
Roffler, Steve R.
Lu, Ssu-Jung
Cheng, Ta-Chun
Wang, Yun-Ming
Chuang, Chih-Hung
Hsieh, Yuan-Chin
Wang, Yeng-Tseng
Wang, Jaw-Yuan
Weng, Kuo-Yi
Cheng, Tian-Lu
生物科技學系
Department of Biological Science and Technology
公開日期: 14-十月-2014
摘要: Quantitative pharmacokinetic analysis of methoxy-poly(ethylene glycol) (mPEG) and mPEGylated molecules is important for clinical drug development. Here we developed sensitive sandwich and competitive ELISAs by expressing an anti-mPEG antibody on the surface of fibroblasts for effective capture of mPEG molecules in biological samples. alpha-mPEG sandwich ELISA could quantify the higher-molecular-weight of mPEG (2, 5, and 20 kDa) and mPEGylated molecules. alpha-mPEG cell-based competitive ELISA was developed to measure the lower-molecular-weight of mPEG molecules (559, 750, and 1000 Da) at nanomolar levels. In addition, alpha-mPEG cell-based ELISA was unaffected by the presence of 10% human serum or murine serum. We further demonstrate that the alpha-mPEG cell-based ELISA determined similar pharmacokinetics of mPEG(5K) as traditional gamma counting of I-131-mPEG(5K). The alpha-mPEG cell-based ELISA may provide an accurate, high sensitivity and easy-to-use tool for directly measuring mPEG and mPEGylated molecules in complex biological samples to accelerate the clinical development of mPEG drugs.
URI: http://dx.doi.org/10.1021/ma501156r
http://hdl.handle.net/11536/25331
ISSN: 0024-9297
DOI: 10.1021/ma501156r
期刊: MACROMOLECULES
Volume: 47
Issue: 19
起始頁: 6880
結束頁: 6888
顯示於類別:期刊論文