Neutron reflectometry as a powerful tool to elucidate membrane interactions of drug delivery systems

The last couple of decades have seen an explosion of novel colloidal drug delivery systems, which have been demonstrated to increase drug efficacy, reduce side-effects, and provide various other advantages for both smallmolecule and biomacromolecular drugs. The interactions of delivery systems with biomembranes are increasingly recognized to play a key role for efficient eradication of pathogens and cancer cells, as well as for intracellular delivery of protein and nucleic acid drugs. In parallel, there has been a broadening of methodologies for investigating such systems. For example, advanced microscopy, mass-spectroscopic "omic"-techniques, as well as small -angle X-ray and neutron scattering techniques, which only a few years ago were largely restricted to rather specialized areas within basic research, are currently seeing increased interest from researchers within wide application fields. In the present discussion, focus is placed on the use of neutron reflectometry to investigate membrane interactions of colloidal drug delivery systems. Although the technique is still less extensively employed for investigations of drug delivery systems than, e.g., X-ray scattering, such studies may provide key mechanistic information regarding membrane binding, re-modelling, translocation, and permeation, of key importance for efficacy and toxicity of antimicrobial, cancer, and other therapeutics. In the following, examples of this are discussed and gaps/opportunities in the research field identified.