Rapidly profiling blood–brain barrier penetration with liposome EKC

Abstract

This report intended to study the potential of liposome EKC (LEKC) as a convenient and high-throughput screening tool to assess drug penetration across the blood-brain barrier (BBB). The retention factors (k) of 24 structurally diverse compounds were determined with LEKC and vesicle EKC (VEKC), respectively. Principal component analysis of the steady-state concentrations ratio of compounds in the brain and in the blood expressed as log BB, log k(LEKC), log k(VEKC), and other lipophilic descriptors including octanol/water partition coefficient (Clog P), octanol/water distribution coefficients (log D(7.4)), and polar surface area (PSA), showed the maximum similarity of partitioning processes in LEKC to drug penetration across the BBB. Furthermore, the log BB were correlated with the above five lipophilic descriptors, and the results showed that log k(LEKC) gave the better correlation coefficient (r(2) = 0.811, p <0.0001) than those of log D(7.4), Clog P, PSA, and log k(VEKC) (r(2) = 0.730, 0.672, 0.627, and 0.620, p <0.0001). This is the first report of the use of LEKC as a promising rapid tool to profile drug penetration across the BBB.

Compositional effects on electrophoretic and chromatographic figures of merit in electrokinetic chromatography with cetyltrimethylammonium bromide/sodium octyl sulfate vesicles as the pseudostationary phase. Part 1: Effect of the phase ratio

“…The bilayer structure of vesicles resembles that of cell membranes, and although many components of the latter such as peripheral and integral membrane proteins, ionchannels, etc., are typically not included by design in vesicle PSPs for a variety of reasons (increased cost, complexity, lack of commercial availability), both surfactant-and phospholipid-based vesicles have nevertheless proven to be useful for modeling a number of biological and nonbiological processes [50][51][52][53] including the prediction/estimation of drug absorption [54], blood-brain barrier penetration [55], intestinal permeability [56], drug interactions with lipid bilayers [53,57,58], protein-liposome interactions [59], octanolwater partitioning [45,60,61], etc.…”

Drug–liposome distribution phenomena studied by capillary electrophoresis‐frontal analysis

“…Also, CE has been used to assess liposomal drug delivery systems in a few cases [18][19][20][21][22]. Liposomes have, however, primarily been introduced into capillaries in studies directed at estimating drug lipophilicity in relation to membrane permeability properties [2][3][4][5][23][24][25][26][27][28]. These studies have been conducted using the liposomes as a pseudostationary phase, i.e., by EKC [2-5, 23-26, 28] or by CEC [27].…”

“…This is due to the structural resemblance of liposomes and cell membranes and their use as drug delivery vehicles. Like biological membranes liposomes consist of a lipid double layer, liposomes may therefore be used as models for the study of drugmembrane adsorption, distribution, and permeation [1][2][3][4][5]. Liposomal drug delivery technology has over the years advanced and marketed drug products using liposomes as the delivery vehicle are available [6][7][8].…”

Liposomes in chromatography

“…The correlation coefficient of the logk-logBBB relationship was R 2 = 0.811. LEKC is a promising, rapid tool to determine drug penetration across the BBB (Wang et al, 2007a). An LEKC method has been employed for the prediction of human drug adsorption.…”