Experimental Methods to Study the Mechanisms of Interaction of Lipid Membranes with Low-Molecular-Weight Drugs
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EW ARTICLE
Experimental Methods to Study the Mechanisms of Interaction of Lipid Membranes with Low-Molecular-Weight Drugs I. M. Le-Deygena, 1, A. A. Skuredinaa, and E. V. Kudryashovaa aChemistry
Department, Moscow State University, Moscow, 119991 Russia
Received February 8, 2020; revised February 20, 2020; accepted February 22, 2020
Abstract—The review is devoted to methods for studying how lipid membranes interact with low-molecularweight drugs. The following methods are considered in the review: IR and EPR spectroscopy, fluorescence analysis, differential scanning calorimetry, and microscopy methods. Methods for characterizing the size and charge of vesicles are also considered: dynamic light scattering and nanoparticle tracking analysis. Methods are divided into those requiring additional labels and label-free. An important objective of the review is to find the optimal research strategy by selecting informative, modern approaches to studying the interactions of drugs with lipid membranes, as well as analyze the latest achievements of instrumental methods. Keywords: liposomes, IR spectroscopy, EPR spectroscopy, fluorescence methods, differential scanning calorimetry DOI: 10.1134/S1068162020040123
INTRODUCTION The development of new biologically active compounds and dosage forms poses significant questions for modern science related to the safety and efficiency of therapy. Incorporation of the active substances in lipid-based delivery systems allows one to combat the pronounced side effects of drugs and increases bioavailability and biocompatibility of the drugs. Thus, elucidation of the drug–membrane interaction and the effect of the active molecule on physicochemical properties of the bilayer are among the key tasks in creating new dosage forms. The toolkit of physicochemical methods used for these purposes is extensive. However, an avalanchelike increasing number of publications on this issue necessitates a deep analysis of the accumulated data in order to discover new complex approaches to studying the interaction of lipid membranes with low-molecular-weight drugs. This review is devoted to the analysis of the latest achievements of instrumental methods for studying
lipid systems. Methods that require a label and labelfree ones are considered separately. Methods that do not require the introduction of a label include classical approaches, such as differential scanning calorimetry (DSC), atomic force microscopy (AFM), scanning electron microscopy (SEM), and cryoelectron microscopy, and relatively new ones, for example, the small-angle X-ray scattering, Fourier transform infrared spectroscopy, environmental scanning electron microscopy, and free electron laser diffraction.
Abbreviations: 16-DSA, 16-doxylstearic acid; 5-DSA, 5-doxylsteraic acid; AFM, atomic force microscopy; DPPC, dipalmitoylphosphatidylcholine; DSC, differential scanning calorimetry; DLS, dynamic light scattering; CL, cardiolipin; MR, mass ratio; SAXS, small angle X-ray scattering; ATIR, attenuated total internal reflection; NTA, nanoparti
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