TY - JOUR
T1 - Surface plasmon resonance studies of the direct interaction between a drug/intestinal brush border membrane
AU - Kim, Kwangmeyung
AU - Cho, Sungpil
AU - Park, Jae Hyung
AU - Byun, Youngro
AU - Chung, Hesson
AU - Kwon, Ick Chan
AU - Jeong, Seo Young
N1 - Funding Information:
This study was supported by Grant No. 01-PJ11-PG9-01NT00-0022 from the Ministry of Health and Welfare, Korea.
PY - 2004/7
Y1 - 2004/7
N2 - Purpose.We describe here a new method to estimate the oral drug permeability from the small intestine using surface plasmon resonance (SPR) technology. The interaction between drugs and brush border membrane (BBM) surfaces immobilized on biosensor chip were evaluated by measuring the SPR response signal. Methods. BBM vesicles, isolated from Sprague-Dawley (SD) rats, were immobilized onto the L1 chip composed of dextran derivatives with modified lipophilic residues. A SPR (BIAcore 3000) was used with L1 chip, and it was carried out in a running buffer, HEPES-buffered saline containing 0.1% DMSO. Fourteen drugs for the SPR experiments were flowed over the BBM immobilized L1 chip, and the response levels according to the BBM surfaces were evaluated directly in a continuous flow system. Results. The immobilized BBM surface on L1 chip was very stable, and it was regenerated by injecting a new BBM vesicle solution. It was evident that drug binding events, using BBM surfaces, directly provides information that predicts the Fa value in human for transcellularly absorbed drugs. The throughput to assay each drug at a single concentration is 100 drugs for 24 h. Conclusions. The interaction between drugs and small intestinal surfaces was successfully assayed using SPR technology, and this SPR analysis exhibited advantages: lack of labeling requirements, the real-time acquirement of various results, and the repeated use for various drugs.
AB - Purpose.We describe here a new method to estimate the oral drug permeability from the small intestine using surface plasmon resonance (SPR) technology. The interaction between drugs and brush border membrane (BBM) surfaces immobilized on biosensor chip were evaluated by measuring the SPR response signal. Methods. BBM vesicles, isolated from Sprague-Dawley (SD) rats, were immobilized onto the L1 chip composed of dextran derivatives with modified lipophilic residues. A SPR (BIAcore 3000) was used with L1 chip, and it was carried out in a running buffer, HEPES-buffered saline containing 0.1% DMSO. Fourteen drugs for the SPR experiments were flowed over the BBM immobilized L1 chip, and the response levels according to the BBM surfaces were evaluated directly in a continuous flow system. Results. The immobilized BBM surface on L1 chip was very stable, and it was regenerated by injecting a new BBM vesicle solution. It was evident that drug binding events, using BBM surfaces, directly provides information that predicts the Fa value in human for transcellularly absorbed drugs. The throughput to assay each drug at a single concentration is 100 drugs for 24 h. Conclusions. The interaction between drugs and small intestinal surfaces was successfully assayed using SPR technology, and this SPR analysis exhibited advantages: lack of labeling requirements, the real-time acquirement of various results, and the repeated use for various drugs.
KW - drug fraction absorbed
KW - intestinal brush border membrane
KW - oral drug permeability
KW - surface plasmon resonance
UR - http://www.scopus.com/inward/record.url?scp=3242688104&partnerID=8YFLogxK
U2 - 10.1023/B:PHAM.0000033011.56536.c3
DO - 10.1023/B:PHAM.0000033011.56536.c3
M3 - Article
C2 - 15290865
AN - SCOPUS:3242688104
SN - 0724-8741
VL - 21
SP - 1233
EP - 1238
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 7
ER -