title: Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations.
abstract: Lipid membranes work as barriers, which leads to inevitable drug-membrane interactions in vivo. These interactions affect the pharmacokinetic properties of drugs, such as their diffusion, transport, distribution, and accumulation inside the membrane. Furthermore, these interactions also affect their pharmacodynamic properties with respect to both therapeutic and toxic effects. Experimental membrane models have been used to perform in vitro assessment of the effects of drugs on the biophysical properties of membranes by employing different experimental techniques. In in silico studies, molecular dynamics simulations have been used to provide new insights at an atomistic level, which enables the study of properties that are difficult or even impossible to measure experimentally. Each model and technique has its advantages and disadvantages. Hence, combining different models and techniques is necessary for a more reliable study. In this review, the theoretical backgrounds of these (in vitro and in silico) approaches are presented, followed by a discussion of the pharmacokinetic and pharmacodynamic properties of drugs that are related to their interactions with membranes. All approaches are discussed in parallel to present for a better connection between experimental and simulation studies. Finally, an overview of the molecular dynamics simulation studies used for drug-membrane interactions is provided.
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lopes
authors.affiliation: Institute of Thermal Separation Processes, Hamburg University of Technology, Germany. Electronic address: jakobtorweihen@tuhh.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Jakobtorweihen
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.affiliation: INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Portugal; IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Gandra, PRD, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: UCIBIO, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000818:Animals; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D004364:Pharmaceutical Preparations / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D004364:Pharmaceutical Preparations
keywords: Biophysics; Drug-membrane interactions; Membrane models; Molecular dynamics simulations; Therapeutic and toxic effects