High-throughput measurement of drug–cyclodextrin kinetic rate constants by a small molecule microarray using surface plasmon resonance imaging†
Applications of small molecule microarrays (SMMs) has been extensively studied but have been limited to the screening of small molecule inhibitors. Here for the first time, we conjugated SMMs with label free surface plasmon resonance imaging (SPRi) for measurement of kinetic parameters for drug–cyclodextrins interactions in high-throughput manner. A collection of insoluble drugs was immobilized onto biosensor surface using photo-cross-linked technique to form SMMs. A highly sensitive and recently reported surface chemistry based on surface initiated polymerization chemistry was used for SMMs fabrication. In total, 38 insoluble drugs were evaluated for their interaction profile and kinetic rate constants against 5 different types of cyclodextrins (CDs) including, α-CD, β-CD, γ-CD, 2-hydroxylpropyl β-CD (HP-β-CD) and sulphobutyl-ether-β-CD (SBE-β-CD). For the supramolecular drug–CD interaction kinetics, the response magnitude and detailed kinetic parameters were calculated and presented in the article. The presented method described a label free and high-throughput technique for real time measurement of kinetic constants for drug–CDs interactions which will assist the selection and use of different CDs in number of different applications.