@article{carrozzino_khaledi_2005, title={PH effects on drug interactions with lipid bilayers by liposome electrokinetic chromatography}, volume={1079}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2005.04.008}, abstractNote={Liposome electrokinetic chromatography (LEKC) provides convenient and rapid methods for studying drug interactions with lipid bilayers using liposomes as a pseudostationary phase. LEKC was used to determine the effects of pH on the partitioning of basic drugs into liposomes composed of zwitterionic phosphatidylcholine (PC), anionic phosphatidylglycerol (PG), and cholesterol, which mimic the composition of natural cell membranes. An increase in pH results in a smaller degree of ionization of the basic drugs and consequently leads to a lower degree of interaction with the negatively charged membranes. From the LEKC retention data, the fractions of drugs distributed in the bulk aqueous and the liposome phase were determined at various pH values. Finally, lipid mediated shifts in the ionization constants of drugs were examined.}, number={1-2}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Carrozzino, JM and Khaledi, MG}, year={2005}, month={Jun}, pages={307–316} }
 @article{carrozzino_khaledi_2004, title={Interaction of basic drugs with lipid bilayers using liposome electrokinetic chromatography}, volume={21}, ISSN={["1573-904X"]}, DOI={10.1007/s11095-004-7685-3}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} This study explores factors influencing the interactions of positively charged drugs with liposomes using liposome electrokinetic chromatography (LEKC) for the development of LEKC as a rapid screening method for drug-membrane interactions. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Liposomes were prepared and the retention factors were measured for a series of basic drugs under a variety of buffer conditions, including various buffer types, concentrations, and ionic strengths as well as using different phospholipids and liposome compositions. LEKC retention is compared with octanol-water partitioning. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} The interaction of ionizable solutes with liposomes decreased with increasing ionic strength of the aqueous buffer. The type of buffer also influences positively charged drug partitioning into liposomes. Varying the surface charge on the liposomes by the selection of phospholipids influences the electrostatic interactions, causing an increase in retention with increasing percentages of anionic lipids in the membrane. Poor correlations are observed between LEKC retention and octanol-water partitioning. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} These studies demonstrate the overall buffer ionic strength at a given pH is more important than buffer type and concentration. The interaction of positively charged drugs with charged lipid bilayer membranes is selectively influenced by the pKa of the drug. Liposomes are more biologically relevant in vitro models for cell membranes than octanol, and LEKC provides a unique combination of advantages for rapid screening of drug-membrane interactions.}, number={12}, journal={PHARMACEUTICAL RESEARCH}, author={Carrozzino, JM and Khaledi, MG}, year={2004}, month={Dec}, pages={2327–2335} }