Surface active drugs: self-association and interaction with membranes and surfactants. Physicochemical and biological aspects

Abstract

Many pharmacologically active compounds are of amphiphilic (or hydrophobic) nature. As a result, they tend to self-associate and to interact with biological membranes. This review focuses on the self-aggregation properties of drugs, as well as on their interaction with membranes. It is seen that drug-membrane interactions are analogous to the interactions between membranes and classical detergents. Phenomena such as shape changes, vesiculation, membrane disruption, and solubilization have been observed. At the molecular level, these events seem to be modulated by lipid flip-flop and formation of non-bilayer phases. The modulation of physicochemical properties of drugs by self-association and membrane binding is discussed. Pathological consequences of drug-membrane interaction are described. The mechanisms of drug solubilization by surfactants are reviewed from the physicochemical point of view and in relation to drug carrying and absorption by the organism.

Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles

“…Two additional tricyclic compounds, clozapine (13) and acriflavine (14), had minimal effect at 100 M (Fig. 5B), as did five cationic amphiphiles compounds that lack a tricyclic ring structure, including tetracaine (15), haloperidol (16), ifenprodil (17), U18666A (18), and diphenhydramine (19) (Fig. 5C).…”

“…To test the hypothesis that the conformation of mammalian SCAP might change in response to membrane properties, we tested the effects of chlorpromazine and imipramine, two prototypical cationic amphiphiles that are known to perturb membrane structure (10,(16)(17)(18). We asked whether these compounds might alter SCAP conformation in the in vitro trypsin digestion assay and whether the response to these drugs might be enhanced by Insig-1 coexpression.…”

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

“…Such action, however, requires a high SOD mimic/lipid ratio (107) that cannot be achieved at the concentrations usually used. Further, no signs of membrane damage were detected when amphiphilic metalloporphyrins were tested at concentrations of approximately 50 lM (Benov et al, unpublished observation).…”

Comparison of paclitaxel penetration in normal and cancerous cervical model monolayer membranes

“…The interaction between pharmacologically active compounds and the cell membrane plays a fundamental role in the pharmacokinetics of the drug [1]. The essential condition of attaining a therapeutic effect of the drug is its penetration to the site of action at a suitable concentration [2].…”