Biophysical Interactions with Model Lipid Membranes: Applications in Drug Discovery and Drug Delivery

Abstract

The transport of drugs or drug delivery systems across the cell membrane is a complex biological process, often difficult to understand because of its dynamic nature. In this regard, model lipid membranes, which mimic many aspects of cell-membrane lipids, have been very useful in helping investigators to discern the roles of lipids in cellular interactions. One can use drug-lipid interactions to predict pharmacokinetic properties of drugs, such as their transport, biodistribution, accumulation, and hence efficacy. These interactions can also be used to study the mechanisms of transport, based on the structure and hydrophilicity/hydrophobicity of drug molecules. In recent years, model lipid membranes have also been explored to understand their mechanisms of interactions with peptides, polymers, and nanocarriers. These interaction studies can be used to design and develop efficient drug delivery systems. Changes in the lipid composition of cells and tissue in certain disease conditions may alter biophysical interactions, which could be explored to develop target-specific drugs and drug delivery systems. In this review, we discuss different model membranes, drug-lipid interactions and their significance, studies of model membrane interactions with nanocarriers, and how biophysical interaction studies with lipid model membranes could play an important role in drug discovery and drug delivery.

Centrifugation-based assay for examining nanoparticle–lipid membrane binding and disruption

“…Firstly, silver nanoparticles are important antimicrobial agents. [48][49][50][51][52] AgNPs are able to destroy bacterial cell walls, to trigger conformational changes of the ion channel, to cause changes of channel opening and dysfunctions. Therefore understanding silver nanoparticle -membrane interactions is essential to understand their toxic effects on both human health and the environment.…”

A mechanistic view of lipid membrane disrupting effect of PAMAM dendrimers

“…The interaction between cell membranes and nanocarriers, such as dendrimers, is very important, because in the most cases carriers have to get across the lipid bilayer without disrupting it. Previous studies based on atomic force microscopy (AFM) [12][13][14][15][16][17] isothermal titration calorimetry (ITC), fluorescence correlated spectroscopy (FCS) [17][18], in vitro experiments [13,[19][20] and molecular dynamics simulations (MD) [14,17,[21][22][23][24] showed that cationic dendrimers disrupt lipid bilayers by forming holes on the bilayer surface and may remove lipids from it. The degree of the disruption depends on the size and charge of the dendrimer.…”

“…Liposomes are widely used as model systems of biological membranes, since both contain lipid bilayers as their basic structural unit [12]. This way, investigating the effect of foreign molecules on the structure and thermal behavior of liposomes, we can obtain basic information on the physicochemical level of toxicity.…”

Low pH Enhances the Action of Maximin H5 against Staphylococcus aureus and Helps Mediate Lysylated Phosphatidylglycerol-Induced Resistance

“…It is generally accepted that the interaction with the CM of target bacteria is an essential step in the antimicrobial action of AMPs [13][14][15][16][17] and interactions of this type have been investigated using a variety of model membranes [18][19][20][21][22][23] . These model membranes are usually formed from lipid mixtures with a head-group composition that reflects the molar ratio of the major lipids in the bacterial membrane, namely PE, phosphatidylglycerol (PG), Lys-PG and cardiolipin (CL).…”