Colloids and Surfaces B: Biointerfaces 69 (2009) 116–121 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Structural and calorimetrical studies of the effect of different aminoglycosides on DPPC liposomes Ágnes Oszlánczi a , Attila Bóta b,∗,1 , Gábor Czabai a , Erwin Klumpp c a Department of Physical Chemistry and Materials Science, Budapest University of Technology and Economics, H-1521 Budapest, Hungary b Chemical Research Centre – Hungarian Academy of Sciences, Institute of Nanochemistry and Catalysis, HU-1025 Budapest, Pusztaszeri út 59-67., Hungary c Agrosphere Institute, Research Centre, D-52425 Jülich, Germany article info Article history: Received 30 June 2008 Received in revised form 17 November 2008 Accepted 18 November 2008 Available online 25 November 2008 Keywords: Aminoglycosides DPPC liposomes DSC Small- and wide-angle X-ray scattering (SWAXS) Unbinding abstract The effects of tobramycin, spectinomycin and streptomycin on 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC)/water vesicle system were studied by using differential scanning calorimetry (DSC) and simultaneous small- and wide-angle X-ray scattering (SWAXS) in the 0–1 lipid/aminoglycoside molar range. The changes in enthalpy between the thermally adjacent phases are decreased, but the pace of decrease is totally different for the three investigated AGs. The alterations in the lamellar arrangement and the chain packing are rather tendentious and are extended by increased AG concentrations depend- ing on the type of the AG. In the case of tobramycin and streptomycin, still sharp Bragg peaks of SAXS curves shift to smaller values of the scattering variable, while spectinomycin results in an entire loss of multilayer correlation representing an increased amount of unbound bilayers. © 2008 Elsevier B.V. All rights reserved. 1. Introduction The members of the aminoglycoside class of antibiotics have a wide spectrum of antimicrobial activity [1]. Most of the clin- ically important Gram-negative [1,2], and as well some of the Gram-positive [1] bacterial infections are treated by these powerful drugs. The major problems associated with these antibiotics are the oto- and nephrotoxicity in humans [2,3], and the drug-resistance of the pathogens that have aminoglycoside-modifying enzymes [1]. In human beings these molecules are taken up by proximal tubu- lar cells and are accumulated in lysosomes [3,4]. Several researchers used negatively charged liposomes in a low pH environment to model lysosomal circumstances and examine their interaction with aminoglycosides. They have found a specific interaction between phosphatidylinositol diphosphate (PIP2) – a negatively charged lipid – and aminoglycosides (AGs) [4–6]. In vitro [7], and in vivo [8] studies have shown that AGs bind to PIP2 molecules in the bilayer of both the biological and artificial membranes, and that the AG-PIP2 complexes inhibit the activities of lysosomal phospholipases [4]. The inhibition of the breakdown of different phospholipids causes ∗ Corresponding author. E-mail address: abota@mail.bme.hu (A. Bóta). 1 Leave from Budapest University of Technology and Economics, Dep. of Phys. Chem. and Mat. Sci. phospholipidosis which is considered to be the first phase of toxic- ity [4,9]. The stability of the AG-PIP2 complex and its consequence, the toxic effect are different, depending on the type of the AG [4–6]. The stability of the complex is related to electrostatic interactions, but hydrophobic interactions may also exist between the drug and the lipid molecules [6,9,10]. Although extensive work has been done by different research groups on the lipid–AG interactions, several conflicting results have been published. As mentioned before, electrostatic interactions were suggested between AGs and an anionic lipid molecule, the PIP2. These findings were based on gel filtration technique, confor- mational calculations [4,5], and NMR spectroscopy [6]. Structural analysis (freeze-fracture method) has also been used to exam- ine the toxic effect of these antibiotics [11]. Some authors have detected integrity changes in some multilamellar liposome sys- tems by leakage of entrapped molecules [9,10]. The disintegration of the liposomes may be explained by the interaction of the AGs and the hydrophobic domain of the bilayer. Comprehensive research has been carried out to clear up the effect of AGs on model membranes, and only a very weak and slowly proceeding inter- action has been found between the AGs and the lipid molecules [12]. In this study the effect induced by some clinically important AGs on the structural and thermotropical changes of a human model membrane has been presented by differential scanning calorimetry (DSC), and simultaneous small- and wide-angle X-ray scatter- ing (SWAXS) measurements. The characteristic features of the 0927-7765/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.colsurfb.2008.11.010