SPR Biosensor Studies of the Direct Interaction between 27 Drugs and a Liposome Surface:  Correlation with Fraction Absorbed in Humans

Journal of Medicinal Chemistry
2000.0

Abstract

We describe a new method to estimate the fraction of a drug absorbed in the human intestine (Fa) based on biosensor technology. Liposomes are attached to a sensor surface, and the interactions between drugs and liposomes are monitored directly using surface plasmon resonance (SPR) technology, which is sensitive to changes in refractive index at the sensor surface caused by mass changes and does not require chromophoric or radiolabeled compounds. Using 27 compounds with reliable Fa values, we show that this direct binding assay with captured liposomes provides data predicting Fa in humans for drugs using the transcellular absorption route: the majority of substances with Fa > 70% can be identified from liposome binding data, and there are indications that medium absorption (Fa 30-70%) drugs can be identified. Drugs with molecular weight < 200 (where paracellular diffusion is possible) are difficult to classify, but this is a less important limitation as most drugs have MW > 200. The method is flexible (allowing up to three different liposomes in one run), stable (surfaces usable for up to 2 weeks), and high-throughput (100 substances/24 h), making it crucial for drug discovery's secondary screening and lead optimization phases where rapid characterization of intestinal absorption properties (especially discrimination between low and medium/high absorption) is needed.

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