Association and sequestered dissociation of an anticancer drug from liposome membrane: Role of hydrophobic hydration.

Abstract

Herein, the interaction of a potent anticancer drug (Sanguinarine, SG) with dimyristoyl-l-α-phosphatidylglycerol (DMPG) liposome membrane has been investigated at physiological pH. The spectroscopic fluorescence decay results demonstrate a modification of the photophysics of SG within DMPG-encapsulated state leading to preferential stabilization of the iminium ion over the alkanolamine form. This suggests a key role of electrostatic force underlying the interaction. The complex dependence of the thermodynamic parameters on temperature yields a unique finding of a positive heat capacity change (ΔCp) indicating the signature of hydrophobic hydration. The study also demonstrates the application of β-cyclodextrin (βCD) as a prospective host system resulting in release of the DMPG-bound drug. A calorimetric exploration of the DMPG-βCD interaction reveals an intrinsically complex thermodynamics of the process leading to ΔCp > 0 and thus marking the instrumental role of hydrophobic hydration which follows that the DMPG-βCD interaction is accompanied with burial of polar molecular surfaces. A systematic investigation of the diffusion of the drug within various microheterogeneous environments by Fluorescence Correlation Spectroscopy (FCS) categorically reinforces our arguments.