Advances in immobilized artificial membrane (IAM) chromatography for novel drug discovery

ABSTRACT

Introduction: The development of immobilized artificial membrane (IAM) chromatography has unfolded new perspectives for the use of chromatographic techniques in drug discovery, combining simulation of the environment of cell membranes with rapid measurements.

Areas Covered: The present review describes the characteristics of phosphatidylcholine-based stationary phases and analyses the molecular factors governing IAM retention in comparison to n-octanol-water and liposomes partitioning systems as well as to reversed phase chromatography. Other biomimetic stationary phases are also briefly discussed. The potential of IAM chromatography to model permeability through the main physiological barriers and drug membrane interactions is outlined. Further applications to calculate complex pharmacokinetic properties, related to tissue binding, and to screen drug candidates for phospholipidosis, as well as to estimate cell accumulation/retention are surveyed.

Expert opinion: The ambivalent nature of IAM chromatography, as a border case between passive diffusion and binding, defines its multiple potential applications. However, despite its successful performance in many permeability and drug-membrane interactions studies, IAM chromatography is still used as a supportive and not a stand-alone technique. Further studies looking at IAM chromatography in different biological processes are still required if this technique is to have a more focused and consistent application in drug discovery.

KEYWORDS:

• IAM chromatography
• biomimetic chromatography
• phospholipophilicity
• membrane permeability
• drug-membrane interactions

Article highlights

• IAM chromatography combines simulation of the cell membrane environment with rapid and reproducible measurements.

• IAM retention is governed by both lipophilic and electrostatic interactions and constitutes a border case between passive diffusion and binding.

• The major potential of IAM retention is to model passive transport.

• IAM chromatography can estimate intestinal permeability and BBB penetration in combination with additional physicochemical or molecular descriptors.

• Further IAM chromatographic investigations are needed to scrutinize and characterize the inherent information content in relation to different biological properties

• Further IAM chromatographic investigations are needed for compounds belonging to particular chemical categories and zwitterions.

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Financial and competing interests disclosure

Dr. F. Tsopelas acknowledges financial support through an IKY fellowship of excellence for postgraduate studies via the Greece-Siemens Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.