This work aims to comprehend the physicochemical interaction of etoposide (trade name “VP-16”) with biological membranes using biomembrane models. Surfactants, owing to their remarkable chemical similarity with biomembranes, can be used to simulate the interactions and behavior of VP-16 in biological systems. The present study explores the physicochemical interactions of chemopreventive VP-16 with ionic dodecyltrimethylammonium bromide (DTAB), sodium dodecyl sulfate (SDS), and nonionic TX-100 & Tween-80 surfactants at the molecular level using different techniques. UV-visible spectroscopy results at 298.15 K indicate that both hydrophilic and hydrophobic interactions significantly influence the solubility of the drug in micellar systems. According to the estimated partition coefficient (Kx ) and binding constant (Kb ) obtained from the differential mode of the UV-Vis, VP-16 exhibits better binding and partitioning with nonionic surfactants compared to ionic surfactants. Thermodynamic parameters ( Δ H m o , Δ S m o , & Δ G m o ) are computed from 298.15 K to 318.15 K with a temperature interval of 5 K using conductivity data. The positive values of Δ H m o and Δ S m o and the negative values of Δ G m o indicate the disruption of water structure during the micellization process in the presence of VP-16 and the spontaneous transport of drug molecules into micelles, respectively. Voltammetric data at 298.15 K show that DTAB and TX-100 favor the oxidation of VP-16. This kind of study may be used to modify currently available drugs, design new chemotherapeutics, and formulate effective drug delivery systems to boost the drugs bioavailability.
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