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DSC studies of the interaction between drugs or other biologically active compounds with biomembrane models has often been associated or integrated with other analytical methodologies. The information gained from various techniques can depict the different and complex elements that compose such interactions. This chapter will summarize some recent examples of successfully combining DSC with other physico-chemical methods, such as spectroscopy, chromatography, calorimetry, the Langmuir–Blodgett film technique and microscopy.
The design and development of drugs and new pharmaceutical formulations require a full characterization of the chemical and physicochemical events occurring at the level of the single active ingredients or excipients, as well as their reciprocal interaction. Thermal analysis techniques are among the most widely used methods to achieve this; among them, the Differential Scanning Calorimetry (DSC) technique, in which the thermotropic behaviour of a single substance or mixtures is analyzed as a function of a controlled temperature program. DSC is an accurate and rapid thermo-analytical technique, widely used by the pharmaceutical industry and in drug research to investigate several physico-chemical phenomena, such as polymorphism, melting and crystallization, purity, and drug-excipient interaction; as well as characterizing biomolecules such as genetic material.Drug-biomembrane interaction studies is written by scientists renowned for their work in the field of DSC applications to drug development and delivery, and especially to drug-biomembrane interaction studies. The book combines insights from biochemistry and physiology with those from structural biology, nanotechnology and biothermodynamics, to obtain a complete depiction of cell membranes and their functions. - Summarizes and updates the recent development in a unique handbook format - Consists of a combination of scientific updates within the field - Contains chapters written by some of the highest-level experts in the field of DSC
Antimicrobial agents are from different classes of molecules that suppress multiplication and growth of or kill microorganisms such as bacteria, fungi, or viruses. The precise mechanism of action of some antimicrobial agents is unknown but they must interact with or cross the cell membrane to have an effect. Identification of the damage induced by these compounds is difficult due to the complexity of cell membranes. Studying interactions using membrane models is a first step in obtaining elementary information about the effects of such drugs. We discuss interaction studies in the recent literature that use calorimetric techniques, regarding the mechanism of action or side effects of antimicrobial agents. For interaction studies with mimetic membrane models using DSC analysis, we will try to answer some key questions: (a) Does lipid composition affect the interaction? (b) Does the composition of bilayers influence the secondary structure of a peptide antimicrobial? (c) Does lipid polymorphism influence the activity and toxicity of the molecules? We underline the importance of phospholipids (neutral or anionic) chosen to produce biomembrane vesicles as models for the different studies.
Interest in using DSC to study the interaction between different compounds and biomembrane models has increased in the last 20years. This is confirmed by the number of published research studies concerning the feasibility of investigating the behavior of different molecules, such as local anesthetics, anticancer drugs, anti-inflammatory drugs, antioxidants, antibiotics, peptides, proteins, polymers, surfactants, genetic materials, macromolecules, and also drug delivery systems (DDSs). This chapter provides a general consideration of the current applications of DSC in evaluating the interaction of different biomolecules and biomembrane models, which will be presented more thoroughly in the succeeding chapters. In particular, a detailed description of the DSC technique for studying the interaction of surfactants, genetic materials, polymers, and DDSs with biomembrane models and biomolecule toxicity studies will be provided, taking into consideration the most recent literature.
DSC is a non-invasive experimental technique, which, besides other numerous applications, has been extensively applied in investigating the thermodynamic properties of synthetic and biological membranes. The calorimetric profiles of phase transitions of self-organized lipid membranes can provide valuable information about membrane interactions with biomolecules, pharmaceutical agents, other membranes, etc. The scope of this chapter is to review specific applications of DSC in studying membrane– nucleic acid interactions, which have attracted scientific attention for their biological relevance, as well as for their potential for biotechnological and pharmaceutical advances.
DSC is a straightforward, non-perturbing thermodynamic technique first developed in the early 1960s. The large number of parameters and the high sensitivity has made DSC one of the key calorimetric tools used for investigating thermodynamic properties of biopolymers, proteins, peptides and nucleic acids. There are numerous reviews covering the different macromolecular applications of DSC: this chapter will primarily focus on proteins and nucleic acids.
This chapter describes a method for evaluating the release of a drug by different delivery systems to biomembrane models made of multilamellar and unilamellar vesicles, using DSC techniques. First, different delivery systems as well as biomembrane models are described followed by a detailed description of the experimental protocols that are the basis of the technique. A drug-loaded delivery system is incubated with the biomembrane model and drug release is evaluated by considering the effect of the drug on the biomembrane’s thermotropic behaviour, and comparing the experimental data with those of the free drug. Finally, examples of the application of this technique are given.
Biological membranes consisting of two main components, lipids and proteins, have many important functions in cells. Membrane structure, physical and chemical properties of lipids and proteins, and interactions between them determine membrane functions such as the barrier separating a cell from its environment, selective transport, cell recognition, signalling and compartmentalization of cellular processes. To investigate membrane structure and dynamics, and the interactions between membrane components on a molecular level, simplified artificial models of biological membranes have been developed. Various biophysical techniques are used with these models to study membrane properties and their changes under different environmental factors. This chapter describes common membrane models and some of their applications. There are two groups of models: vesicular models (micelles, bicelles and liposomes) and planar ones (lipid monolayers, supported lipid bilayers, black lipid membranes). The advantages and disadvantages of both types are discussed as well as their usefulness for particular biophysical techniques.
In this chapter we briefly introduce the main physical principles of DSC as well as related techniques. After a quick survey of the more common experimental techniques, we describe the thermodynamics and kinetics of events accompanying a heating/cooling process. We focus on lipid membranes of one or more components. Both the thermotropic and the barotropic behaviours are investigated, as well as the water/lipid ratio. The effect of foreign impurities (hydrophobic molecules, proteins) dissolved in the lipid matrix on DSC thermotropic behaviour is also investigated, either in the ideal mixing model or for non-ideal miscibility. In the poor miscibility limit, lipids and hydrophobic impurities may undergo phase separation. The mechanisms of phase separation are discussed and related to experimental DSC features. Out-of-equilibrium phenomena, such as the different thermotropic behaviour between heating and cooling modes or the kinetics of lipid/water partitioning, are explained using simple models for phase transitions.
Barrier, reservoir, target site - those are but some of the possible functions of biological lipid membranes in the complex interplay of drugs with the organism. A detailed knowledge of lipid membranes and of the various modes of drug-membrane interaction is therefore the prerequisite for a better understanding of drug action. Many of today's pharmaceuticals are amphiphilic or catamphiphilic, enabling them to interact with biological membranes. Crucial membrane properties are surveyed and techniques to elucidate drug-membrane interactions presented, including computer-aided predictions. Effects of membrane interaction on drug action and drug distribution are discussed, and numerous examples are given. This unique reference volume builds on the authors' long experience in the study of drug-membrane interaction. Recommended reading for everyone involved in pharmaceutical research.