Transfer Mechanism of Anthracycline Antibiotics and Their Ion Association with PAMAM Dendrimer at Liquid|Liquid Interfaces**

Abstract

The transfer reaction of anthracycline antibiotics, daunorubicin (DNR) and doxorubicin (DOX), was investigated at the water|1,2‐dichloroethane (DCE) interface. Spectroelectrochemical analysis demonstrated significant changes in the transfer mechanism of anthracycline cations with a slight structural difference across the bare water|DCE interface and the biomimetic interface with a phospholipid layer. The facilitated ion transfer feature was found for both HDNR+ and HDOX+ at the biomimetic interface, where the adsorption process of HDOX+ was observed over a wide potential range at the aqueous side of the interface, that is, the polar headgroup region of the phospholipid layer. The molecular association between the carboxylate‐terminated generation 3.5 polyamidoamine (G3.5 PAMAM) dendrimer and anthracycline derivatives occurred preferentially under neutral pH conditions. The negatively charged G3.5 PAMAM dendrimer induced positive shifts of the transfer potential of anthracycline cations at the water|DCE interface, indicating its ability as potential‐ and pH‐responsive drug carriers.

Voltammetric Study of Lomefloxacin Transfer at the Interface between Two Immiscible Electrolyte Solutions: Ionic Partition, Photodegradation, and Sensing Applications

“…This indicates that the positively charged and neutral LOM were much less soluble in water and 1,2‐DCE, respectively, than those of LVX species. Consequently, the Gibbs energy transfer value of LVX (14.5 kJ mol −1 ) [6] was lower than that of LOM (20.45 kJ mol −1 ), indicating that LOM was more hydrophilic than LVX [1] …”

“…Further analyses of the ionic partition diagram, as shown in Figure 2 alongside a modified approach proposed by Brounched et al [41] . which was further developed by Nagatani et al [1] . and Borgul et al [42] .…”

“…Electrochemical studies of the ion transfer process across a polarized interface between two immiscible electrolyte solutions (ITIES) are a useful platform for understanding the physical, thermodynamic, and pharmacokinetic properties of ionizable antibiotic drug molecules [1–11] . For example, Zanotto et al.…”

Spectroelectrochemical Analysis of Ion Transfer Mechanisms of Mitoxantrone at Liquid|Liquid Interfaces: Effects of Zwitterionic Dendrimer and Phospholipid Layer

“…As shown in Figure a, the peak responses for the ion transfer of HMTX + centered around 0.26 V were positively shifted to 0.39 V in the case of the G2.5 and G3.5 PAMAM dendrimers and the intermediate feature maximized around 0.34 V was measured for the G1.5 dendrimer. The shift of ion transfer potential true( Δ ( normalΔ normalo normalw ϕ tr ) true) by adding dendrimers relates to the ion association energy (Δ G assoc ). ,− normalΔ ( normalΔ normalo normalw ϕ tr ) = Δ o w ϕ tr .25em , MTX den − Δ o w ϕ tr , MTX = − ( Δ G assoc ) pH z F where Δ o w ϕ tr , MTX den and Δ o w ϕ tr , MTX are the transfer potentials of MTX species (HMTX + at pH 7.4) measured in the presence and absence of equimolar dendrimers and z is the charge number of the transferring MTX ion. The Δ G assoc values for HMTX + were evaluated from the PMF signals as −8 kJ mol –1 (G1.5) and −13 kJ mol –1 (G2.5 and G3.5), respectively (Table ).…”

“…The charge transfer reactions of a variety of dendrimers have also been studied at an interface between two immiscible electrolyte solutions (ITIES), where the higher generation dendrimers tend to adsorb to the water|organic interface. − ITIES can be considered as a simple model of biomembrane . A phospholipid monolayer-modified interface is particularly useful for understanding membrane surface reactions such as ion transport and specific adsorption. − Recently, we reported the molecular association behavior between the generation 3.5 (G3.5) PAMAM dendrimer and anthracycline antibiotics, doxorubicin (DOX) and daunorubicin (DNR), at ITIES . The G3.5 PAMAM dendrimer is a zwitterionic compound with interior tertiary amines and terminal carboxylates, and therefore, its net charge varies with the surrounding pH condition.…”