The interactions of drugs with biological and liposomal membranes

点击翻译按钮获取中文摘要

The proposed work aims at establishing quantitative biophysical rules describing the interaction of drugs and other small molecules with biological and liposomal membranes. These are of fundamental interest since virtually all drugs have to interact with membranes; they may bind to membrane receptors, act by changing membrane properties, or need to cross membranes to reach their target. Furthermore, artificial membranes (liposomes) are loaded with drugs for targeted drug delivery and optimized release.We plan to determine and model which and how key properties of the membrane and the additive govern the uptake of the additive, its permeation through the membrane, and changes of membrane properties induced by the additive. The results will shed light on the mechanisms of action of pharmaceutically relevant molecules (e.g., antibiotic peptides, penetration enhancers, anaesthetics) and they will provide rules for the optimization of drugs and drug formulations (including liposomal drug delivery vehicles) regarding their efficacy, selectivity, and pharmacokinetics.To achieve this goal, we plan to apply a number of newly developed, biophysical techniques such as pressure perturbation calorimetry and new assays for titration calorimetry and fluorescence spectroscopy along with established methods.