Abstract
Hydrazones based on mono- and bicyclic terpenoids (verbenone, menthone and carvone) have been investigated in vitro as potential biomembrane penetration enhancers. In this regard, liposomes composed of lecithin or cardiolipin as phospholipid phase components with incorporated fluorescence probes have been prepared using the thin-film ultrasonic dispersion method. The mean particle size of the obtained liposomes, established using laser diffraction, was found to be 583 ± 0.95 nm, allowing us to categorize them as multilamellar vesicles (MLVs) according to their morphology. Pursuant to fluorescence analysis, we may assume a reduction in microviscosity and, consequently, a decrease in the packing density of lecithin and cardiolipin lipids to be the major mechanism of action for terpenoid hydrazones 1–15. In order to determine the molecular organization of the lipid matrix, lipids were isolated from rat strata cornea (SCs) and their interaction with tested compounds was studied by means of Fourier transform infrared spectroscopy. FT-IR examination suggested that these hydrazones fluidized the SC lipids via the disruption of the hydrogen-bonded network formed by polar groups of SC constituents. The relationship between the structure of terpenoid hydrazones and their ability to enhance biomembrane penetration is discussed.
Highlights
The development of novel drug molecules involves the interaction of the compounds with their potential pharmacological targets and a mechanism of drug delivery that can overcome biological barriers such as the skin, blood–brain barrier and cell and nuclear membranes
In this paper, we confirmed the impact of terpenoid hydrazones containing residues of para-substituted phenoxyacetic acid on the molecular organization of the lipid matrix
Fluorescence probe analysis with the use of lecithin and cardiolipin liposomes suggested that terpenoid derivatives decrease phospholipid microviscosity and disrupt their packing density
Summary
The development of novel drug molecules involves the interaction of the compounds with their potential pharmacological targets and a mechanism of drug delivery that can overcome biological barriers such as the skin, blood–brain barrier and cell and nuclear membranes. A significant increase in the I1/I3 parameter was predominantly observed after the incorporation of hydrazones with bulky -C(CH3) and -O-C6H5 groups into lipid membranes This growth of the I1/I3 value demonstrates an increase in the polarity of the fluorophore microenvironment, which might be caused by the appearance of hydrophilic clusters in cardiolipin lipid layers. Based on fluorescence analysis, we may suggest a reduction in microviscosity and, a decrease in the packing density of lecithin and cardiolipin lipids, as the major mechanism of action for terpenoid hydrazones with H, Cl or Br atoms in the para-position of the benzene ring. Hydrazones containing bulky -C(CH3) and -OC6H5 groups were found to increase the membrane polarity via the appearance of hydrophilic clusters or via the penetration of water molecules into the lipid layers of cardiolipin liposomes
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