Quantitative Retention‐Activity Relationship Studies by Liposome Electrokinetic Chromatography to Predict Skin Permeability

Abstract

Liposome electrokinetic chromatography (LEKC) provides a simple and facile approach for drug membrane interactions using liposome as a pseudostationary phase. This study evaluated the potential of LEKC for high-throughput skin permeability profiled as an in vitro technique. A quantitative retention-activity relationship (QRAR) model for the estimation of skin permeability was proposed. For the 16 structurally diverse chemicals, lg k correlated well with permeability values (R 2 ＝0.886). The predictive ability of the model was evaluated by cross-validation. The result was compared to traditional quantitative structure-activity relationship, QSAR, models using some molecular descriptors and physicochemical parameters. Interestingly, a single LEKC retention parameter was capable of describing the skin permeability, while three variables in QSAR were needed to achieve a similar correlation (R 2 ＝0.704). The QRAR models developed in this paper may be a useful method to screening new chemicals and in the early stage of development and selection of chemicals.

Liposomes in chromatography

“…It was found that the predictive value of QSAR calculations was lower that that of QRAR (R 2 = 0.704). LEKC and QRAR can be successfully applied for the prediction of skin permeation capacity and for the screening of new compounds (Xian et al, 2008a).…”

A Novel Liposomal Dexamethasone Palmitate Formulation and Anti‐inflammatory Effects on Mice

“…At present, there are several different methods that have been used to prepare liposome. 5,6 In this study, we report a study of a novel dexamethasone formulation by performing the controlled process of acute toxicity and anti-inflammation with dexamethasone sodium phosphate injection, dexamethasone palmitate liposome and dexamethasone palmitate long circulating liposome on mice.…”

Linear Free Energy Relationship Analysis of Retention Factors in Cerasome Electrokinetic Chromatography Intended for Predicting Drug Skin Permeation

“…Compared with IAM and MEKC, LEKC provides not only the measurement advantages, such as speed, small sample amount, automation, lack of sample purity requirement, and high reproducibility, but also a distinct lipophilicity index in pharmacokinetic studies, as liposomes possess spherical lipid bilayer microstructures that make them more suitable models for the dynamic and fluid bilayer environment of biomembranes. LEKC has been used to evaluate the penetration of chemicals through skin in recent years and the derived quantitative structure–permeability relationship models showed adequate predictive ability for skin permeation, as log K p 9,10…”