Development of an Anti-Methoxy Poly(ethylene glycol) (α-mPEG) Cell-Based Capture System to Measure mPEG and mPEGylated Molecules

• Published in: Macromolecules Vol. 47; no. 19; pp. 6880 - 6888
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14.10.2014
• Subjects: Analysis and structure; Applied sciences; Biological and medical sciences; Exact sciences and technology; General pharmacology; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymer industry, paints, wood; Properties and testing; Technology of polymers; Intravenous administration; Control release polymer; Rodentia; Drug carrier; Prodrug; Experimental study; Ethylene oxide polymer; In vivo; Vertebrata; Sensitivity; Mammalia; Analysis method; Mouse; Pharmacokinetics; ELISA assay; Quantitative analysis
• ISSN: 0024-9297; 1520-5835
• DOI: 10.1021/ma501156r

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. α-mPEG sandwich ELISA could quantify the higher-molecular-weight of mPEG (2, 5, and 20 kDa) and mPEGylated molecules. α-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, α-mPEG cell-based ELISA was unaffected by the presence of 10% human serum or murine serum. We further demonstrate that the α-mPEG cell-based ELISA determined similar pharmacokinetics of mPEG5K as traditional gamma counting of 131I-mPEG5K. The α-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.