Research ArticlesRapid determination of liposome–water partition coefficients (Klw) using liposome electrokinetic chromatography (LEKC)
Section snippets
INTRODUCTION
There has been a great deal of interest in investigating partitioning behavior of solutes into lipid bilayers and biological activity.1,2 Due to difficulties associated with investigating solute interactions with biological cell membranes, different chemical models have been proposed in Quantitative Structure Activity Relationships (QSAR) studies. Collander showed the distribution of drugs in membranes was related to their partition coefficients in aqueous–organic solvents.3 Over the past 4
Chemicals
Dipalmitoyl‐L‐α‐phosphotidylcholine (DPPC), dipalmitoyl‐L‐α‐phosphotidylglycerol (sodium salt) (DPPG), and cholesterol (Chol) were purchased from Sigma Chemical Co. (St. Louis, MO). The acidic form of HEPES (N‐[2‐Hydroxyethyl] piperazine‐N′‐[2‐ethanesulfonic acid]) was purchased from Sigma Chemical Co. (St. Louis, MO), while chloroform and the basic form of HEPES (N‐[2‐Hydroxyethyl] piperazine‐N′‐[2‐ethanesulfonic acid](Na salt)) were purchased from Fluka (Buchs, Switzerland). Sodium Phosphate
PROCEDURES
The capillary was rinsed in the following manner prior to use each day: a 10‐min rinse with Milli‐Q water; a 20‐min rinse with 1.0 M NaOH; a 10‐min rinse with Milli‐Q water; a 10‐min rinse with methanol; another 10‐min rinse with Milli‐Q water; and a 20‐min rinse with the liposome solution. Furthermore, the Milli‐Q water, methanol, 1.0 M NaOH, and liposome solution were all filtered through a 0.45‐μm filter disk (Scientific Resources Inc.) prior to use. The capillary was vacuum‐rinsed with the
Determination of Klw
The retention factors (k) for uncharged solutes were calculated from the retention time data using the following eq. 1where teo is the retention time of the unretained solute (methanol), tr is the retention time of the solute, and tlip is the retention time of the liposome marker (decanophenone).
The liposomes used in this work were Small Unilamelar Vesicles (SUVs) that were composed of 24 % anionic DiPalmitoylPhosphotidylGlycerol (DPPG), 46 % zwitterionic
CONCLUSION
LEKC provides remarkable advantages for investigations of drug interactions with lipid bilayers. It combines the biomimic nature of artitficial lipid bilayer membranes with capabilities of a chromatographic technique such as small sample size, lack of sample purity requirements, speed, and automation. The only shortcoming of this technique is the existence of an elution window that limits the dynamic range for uncharged solutes. This problem can be obviated for charged drugs by using neutrally
Acknowledgements
A research grant from the U.S. National Institutes of Health (GM 38738) is gratefully acknowledged.
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2018, Capillary Electromigration Separation MethodsA novel enantioseparation approach based on liposome electrokinetic capillary chromatography
2017, Journal of Pharmaceutical and Biomedical AnalysisCitation Excerpt :On the other hand, all the enantiomers achieved baseline separation and demonstrated a considerable promotion, including increased Rs and α in the new established LEKC system. According to previous articles [19–23], the interactions between liposomes and selector-enantiomer complexes were achieved via intermolecular forces, including hydrogen-bonding interaction, hydrophobic interaction, electrostatic interaction, polarity interaction and as well, which could contribute to a distribution difference of the complexes between liposomes and the bulk aqueous phase and consequently enhance the enantioselectivity of this new LEKC system. The variation of these above non-covalent forces caused by changes in separation conditions could affect the distribution constant between complexes and liposomes, which influences the chiral separation performance.
The application of open disk-like structures as model membrane and drug carriers
2013, Asian Journal of Pharmaceutical SciencesCitation Excerpt :Khaledi's laboratory studied the molecular interaction mechanisms of various types of solutes and biomembrane in LEKC [10,11]. Wang et al. have used LEKC to predict drug oral absorption and blood–brain barrier penetration rapidly [12,13]. Retention factors, also referred to as capacity factors, determined with MEKC and MEEKC, have been correlated with the octanol–water partition coefficient (Po/w), which in turn is used to estimate membrane permeability [14,15].