Liposome/water lipophilicity: Methods, information content, and pharmaceutical applications

Abstract

This review discusses liposome/water lipophilicity in terms of the structure of liposomes, experimental methods, and information content. In a first part, the structural properties of the hydrophobic core and polar surface of liposomes are examined in the light of potential interactions with solute molecules. Particular emphasis is placed on the physicochemical properties of polar headgroups of lipids in liposomes. A second part is dedicated to three useful methods to study liposome/water partitioning, namely potentiometry, equilibrium dialysis, and (1)H-NMR relaxation rates. In each case, the principle and limitations of the method are discussed. The next part presents the structural information encoded in liposome/water lipophilicity, in other words the solutes' structural and physicochemical properties that determine their behavior and hence their partitioning in such systems. This presentation is based on a comparison between isotropic (i.e., solvent/water) and anisotropic (e.g., liposome/water) systems. An important factor to be considered is whether the anisotropic lipid phase is ionized or not. Three examples taken from the authors' laboratories are discussed to illustrate the factors or combinations thereof that govern liposome/water lipophilicity, namely (a) hydrophobic interactions alone, (b) hydrophobic and polar interactions, and (c) conformational effects plus hydrophobic and ionic interactions. The next part presents two studies taken from the field of QSAR to exemplify the use of liposome/water lipophilicity in structure-disposition and structure-activity relationships. In the conclusion, we summarize the interests and limitations of this technology and point to promising developments.

Determination of liposome–buffer distribution coefficients of charged drugs by capillary electrophoresis frontal analysis

“…Liposomes consisting of phospholipid bilayers share structural similarities with biological membranes and therefore have been used as tools to model drug-membrane interactions and to deliver drugs [1][2][3].…”

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

“…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].…”

Drug-delivery and multifunction possibilities of hypocrellin photosensitizers

“…HB in liposome is completely enclosed by the bilayer phospholipid membranes, but the R F=A value is far lower than in benzene, suggesting that the environment in liposome is not perfectly hydrophobic for presence of some water molecules in semi-°uid liposome. 77 In comparison, the hydrophobic area in the proteins is not completely closed as in liposome, therefore the R F=A values are lower than in liposome. Particularly, hydrophobic area in polysaccharides is half-open, therefore, it has the lowest R F=A value.…”