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

Sequestration of Drugs from Biomolecular and Biomimicking Environments: Spectroscopic and Calorimetric Studies

“…These observations are indicative of the expulsion of the drug molecules bound to the DMPG-lipid with added βCD [34,86,87]. Such release of the bound drug molecules is also accompanied by a significant reduction in the steady-state fluorescence anisotropy of the DMPG-bound drug in the presence of βCD, indicating the release of motional restrictions of the bound drug molecules [47]. It is pertinent to note that the complex interaction situation here can lead to several possible equilibria, such as the (i) interaction of DMPG lipid with βCD leading to disruption of the compact liposome structure, and (ii) inclusion of the drug molecules within βCD.…”

“…The binding interaction of SG with dimyristoyl-L-α-phosphatidylglycerol (DMPG) lipid is found to be reflected by a sharp enhancement of the fluorescence intensity of the band distinctive of the iminium form of SG (λem~580 nm) together with the diminution of the fluorescence intensity of the band of the alkanolamine form (λem~418 nm) with increasing DMPG concentrations (Figure 6a); a schematic representation of the iminium and alkanolamine forms of SG is given in Scheme 2. This observation suggests that a preferential binding interaction of the cationic (iminium) form of the drug with the anionic surface charge of the lipid (DMPG) is assisted by a stabilizing electrostatic interaction [47]. Figure 6b reveals that with added β-cyclodextrin (βCD), the fluorescence intensity of the iminium form (λem~580 nm) of DMPG-bound SG decreases coupled with an increase in the intensity of the alkanolamine form (λem~418 nm).…”

“…In this section, we discuss the sequestration of small drug molecules bound to liposome membranes by cyclodextrin [47]. Cyclodextrins (CDs) are non-toxic, cyclic sugar polymers, soluble in water and in polar solvents, comprised of a structurally well-defined hydrophobic cavity that can accommodate small "guest" molecules mainly via non-covalent interactions.…”

“…It is pertinent to note that the complex interaction situation here can lead to several possible equilibria, such as the (i) interaction of DMPG lipid with βCD leading to disruption of the compact liposome structure, and (ii) inclusion of the drug molecules within βCD. With a view of the considerably weak interaction of SG with βCD (association constant in the order of ~10 −3 M −1 [82]), the second possibility is rationally discarded [47]. Association and dissociation kinetics.…”

“…Below the CMC, Triton-X 114 is unable to extract the drug molecules from DNA, but beyond its CMC, the surfactant is found to extract the DNA-intercalated safranin O. CD spectroscopy further validated that the secondary structure of DNA is not influenced by Triton-X 114 at both premicellar and micellar concentrations, thereby making the non-ionic surfactant an effective drug-sequestrating probe [32]. Different drug-sequestrating agents for various biomolecular/bio-replicating systems are tabulated in Table 1 [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. In this section, we will discuss the mechanism of the sequestration of Harmane (HM) bound to herring sperm DNA, using the cationic surfactant CTAB [29].…”