Surface plasmon resonance studies of the direct interaction between a drug/intestinal brush border membrane.
OBJECTIVE
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.
Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea.
Kwangmeyung
K
Kim
Sungpil
S
Cho
Jae Hyung
JH
Park
Youngro
Y
Byun
Hesson
H
Chung
Ick Chan
IC
Kwon
Seo Young
SY
Jeong
D000818:Animals; D015374:Biosensing Techniques; D006801:Humans; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism* / Q000648:ultrastructure; D008871:Microvilli / Q000378:metabolism; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D040081:Protein Array Analysis; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020349:Surface Plasmon Resonance / Q000379:methods*; D013997:Time Factors
D004364:Pharmaceutical Preparations