Do surface-based match solution-based techniques? The case of drug-liposome interaction

Abstract

The aim of the study is to check if the information about drug/liposome interactions provided by Surface Plasmon Resonance (SPR) is comparable with that provided by potentiometry in which liposomes are not immobilized on a solid support. To reach our aim we apply QSPR and BR analysis to data extracted from the literature and carefully inspected for their reliability. Results show that log KD (SPR) is governed by a different balance of intermolecular interactions than log Dlip (potentiometry).

Block relevance (BR) analysis and polarity descriptors in property-based drug design

“…Overall, BR analysis shows that log K w IAM is essentially related to the dimensions of the molecules. [2] Biomimetic chromatographic index log K mucin [19] Biomimetic combined chromatographic index Δlog K W IAM [2] Biophysical method Log K D (SPR) [20] Chromatographic index log k' C18 [5] Chromatographic index log k' Ph [5] Chromatographic index log k' CN-RP [5] Chromatographic index log k' OH-RP [5] Chromatographic index log k' CN-RP [5] Chromatographic index log k' OH-RP [5] Chromatographic index log k' NH2-NP [5] Chromatographic index log k' HILIC [5] Chromatographic index log k' EPSA [21] Chromatographic index log k'80 PLRP-S [22] Chromatographic index ElogD [22] Combined partition coefficient Δlog P oct-tol [6] Computed descriptor TPSA [21] Computed distribution coefficient Calc log D oct [23] Computed partition coefficient Calc log P tol [22] Distribution coefficient log D lip [20] Distribution coefficient log D 7.4 oct [2] Partition coefficient log P oct [5] Partition coefficient log P oct [7] Partition coefficient ElogP [7] Partition coefficient log P oct [6] Partition coefficient log P tol [6] Partition coefficient log P oct [2] Permeability rate log P app (RRCK) [21] Permeability rate log P app (Caco-2) [21] Permeability rate log P app (6.5/7.4) [23] Permeability rate log P app (7.4/7.4) [23] As expected, the VIPs/coefficients plots and the BR analysis provide a similar picture, but the BR analysis immediately focuses on the main features that drive the model. It is noteworthy to underline that the two approaches can be combined; using the BR analysis to obtain a general idea of the main interaction governing the property under study and then the VIPs/coefficients plots for a more detailed analysis of the results.…”