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Determination of lipid–water partition coefficient of neutral and ionic drugs by liposome electrokinetic chromatography
- Source :
- ELECTROPHORESIS. 42:1436-1449
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Profiling of lipid-water partition coefficients (KL/W ) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid-water partition coefficients (log KL/W ) of neutral and ionic drugs were determined based on an iterative method. The log KL/W values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient (R2 = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol-water system, immobilized artificial membrane, Caco-2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco-2 cell model, and R2 was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J- were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log KL/W of drugs.
- Subjects :
- Clinical Biochemistry
Synthetic membrane
Ionic bonding
02 engineering and technology
Free-energy relationship
01 natural sciences
Biochemistry
Analytical Chemistry
Electrokinetic phenomena
polycyclic compounds
Humans
Ions
Chromatography
Liposome
Chemistry
Hydrogen bond
fungi
010401 analytical chemistry
technology, industry, and agriculture
Water
Membranes, Artificial
021001 nanoscience & nanotechnology
0104 chemical sciences
Solutions
Partition coefficient
Kinetics
Cholesterol
Membrane
Liposomes
lipids (amino acids, peptides, and proteins)
Caco-2 Cells
0210 nano-technology
Subjects
Details
- ISSN :
- 15222683 and 01730835
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- ELECTROPHORESIS
- Accession number :
- edsair.doi.dedup.....6b81b38b113e5a04bd6964505befef21