Drug Membrane Interactions

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.

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.

This chapter will summarize recent information on cell membranes. Their structure, functions and the role of the various components are discussed, considering both their physiological tasks, such as mechanisms of drug internalization into cells, as well as membrane changes associated with or caused by particular disease states. Later chapters will discuss the possibility of testing biomembrane models to study their interaction with drugs and biological compounds.

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 lipid bilayer's integrity is essential for cell function as it acts as the primary barrier against external molecules like drugs and peptides, which can alter the bilayer's physical properties. This dissertation investigates how amphetamine (AMPH) and methamphetamine (METH), and the charged HIV1-TAT peptide impact the stability of lipid bilayers, using a home-built lipid bilayer apparatus that enables real-time monitoring through electrical and fluorescence measurements. Our findings indicate that AMPH and METH increase the lipid bilayer's ion permeability, with METH having a greater destabilizing effect. High concentrations of these stimulants, akin to levels in blood plasma of individuals with stimulant-related brain injuries, lead to pore formation in the bilayer. The extent of destabilization correlated with the drug concentration. We also studied the translocation dynamics of the charged HIV1-TAT peptide across the lipid bilayer. The analysis of current fluctuations showed that successful translocation of the TAT peptide is concentration-dependent, highlighting the significance of charge in inducing membrane deformation or pore formation. Additionally, molecular dynamic simulations were used to explore AMPH interactions with the lipid bilayer in greater detail. The results revealed AMPH's preferred orientation during interaction and its hydrophobic nature, as evidenced by the larger energy barrier encountered in the hydrophilic head group regions of the lipid bilayer. To complement these findings, we utilized surface-enhanced Raman spectroscopy (SERS) to estimate the concentrations of AMPH within lipid bilayers. The data showed a positive correlation between characteristic peak heights and AMPH concentrations. Moreover, whole-cell patch clamp measurements on neuronal cells were employed to examine AMPH's effects in a more intricate lipid environment. This research contributes to the understanding of how stimulants and charged peptides interact with lipid bilayers, which is vital for insights into their biological impacts and in developing therapeutic interventions.