Immobilised artificial membrane liquid chromatography vs liposome electrokinetic capillary chromatography: Suitability in drug/bio membrane partitioning studies and effectiveness in the assessment of the passage of drugs through the respiratory mucosa

Orzel, Dorota; Ravald, Henri; Dillon, Amy; Rantala, Julia; Wiedmer, Susanne K.; Russo, Giacomo

Abstract

This study pioneers a comparison of the application of biomimetic techniques, immobilised artificial membrane liquid chromatography (IAM LC) and liposome electrokinetic capillary chromatography (LEKC), for the prediction of pulmonary drug permeability. The pulmonary absorption profiles of 26 structurally unrelated drug-like molecules were evaluated using their IAM hydrophobicity index (CHI IAM) measured in IAM LC, and the logarithm of distribution constants (log KLEKC) derived from the LEKC experiments. Lipophilicity (phospholipids) parameters obtained from IAM LC and most LEKC analyses were linearly related to the n-octanol/water partitioning coefficients of the neutral forms (i.e., log Po/w values) to a moderate extent. However, the relationship with distribution coefficients at the experimental pH (7.40) (i.e., log D7.4) were weaker overall for IAM LC data and sigmoidal for some liposome compositions (phosphatidyl choline (PC): phosphatidyl inositol (PI) 85:15 mol% and 90:10 mol%) and concentrations (4 mM) in LEKC. This suggests that phospholipid partitioning supports both hydrophobic and electrostatic interactions occurring between ionised drugs and charged phospholipid moieties. The latter interactions are original when compared to those taking place in the more established n-octanol/water partitioning systems.

A stronger correlation (R2 > 0.65) was identified between the LEKC retention parameters, and the experimental apparent lung permeability (i.e., log Papp values) as opposed to the values obtained by IAM LC. Therefore, LEKC offers unprecedented advantages over IAM LC in simulating cell membrane partitioning processes in the pulmonary delivery of drugs. Although LEKC has the advantage of more effectively simulating the electrostatic and hydrophobic forces in drug/pulmonary membrane interactions in vitro, the technique is unsuitable for analysing highly hydrophilic neutral or anionic compounds at the experimental pH. Conversely, IAM LC is useful for analysing compounds spanning a wider range of lipophilicity. Its simpler and more robust implementation, and propensity for high-throughput automation make it a favourable choice for researchers in drug development and pharmacological studies.

Citation

Orzel, D., Ravald, H., Dillon, A., Rantala, J., Wiedmer, S. K., & Russo, G. (2024). Immobilised artificial membrane liquid chromatography vs liposome electrokinetic capillary chromatography: Suitability in drug/bio membrane partitioning studies and effectiveness in the assessment of the passage of drugs through the respiratory mucosa. Journal of Chromatography A, 1734, Article 465286. https://doi.org/10.1016/j.chroma.2024.465286

• Journal Article Type: Article
• Acceptance Date: Aug 17, 2024
• Online Publication Date: Aug 18, 2024
• Publication Date: 2024
• Deposit Date: Aug 19, 2024
• Publicly Available Date: Aug 19, 2024
• Journal: Journal of Chromatography A
• Print ISSN: 0021-9673
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 1734
• Article Number: 465286
• DOI: https://doi.org/10.1016/j.chroma.2024.465286
• Keywords: biomimetic chromatography, drug/phospholipid interactions, immobilised artificial membrane chromatography, liposome electrokinetic capillary chromatography, pulmonary drug permeability