Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 6880-6888 |
| Number of pages | 9 |
| Journal | Macromolecules |
| Volume | 47 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Oct 14 2014 |
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ASJC Scopus subject areas
- Organic Chemistry
- Materials Chemistry
- Polymers and Plastics
- Inorganic Chemistry
Cite this
Development of an anti-methoxy poly(ethylene glycol) (α-mPEG) cell-based capture system to measure mPEG and mPEGylated molecules. / 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.
In: Macromolecules, Vol. 47, No. 19, 14.10.2014, p. 6880-6888.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Development of an anti-methoxy poly(ethylene glycol) (α-mPEG) cell-based capture system to measure mPEG and mPEGylated molecules
AU - Chuang, Kuo Hsiang
AU - Kao, Chien Han
AU - Roffler, Steve R.
AU - Lu, Ssu Jung
AU - Cheng, Ta Chun
AU - Wang, Yun Ming
AU - Chuang, Chih Hung
AU - Hsieh, Yuan Chin
AU - Wang, Yeng Tseng
AU - Wang, Jaw Yuan
AU - Weng, Kuo Yi
AU - Cheng, Tian Lu
PY - 2014/10/14
Y1 - 2014/10/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907970842&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907970842&partnerID=8YFLogxK
U2 - 10.1021/ma501156r
DO - 10.1021/ma501156r
M3 - Article
AN - SCOPUS:84907970842
VL - 47
SP - 6880
EP - 6888
JO - Macromolecules
JF - Macromolecules
SN - 0024-9297
IS - 19
ER -