Physicochemical characterization of novel 3-carboxymethyl-bile salts, as permeability and solubility enhancers

New bile acid derivatives are synthesized: 3-(carboxymethyl)-50-chol-3-ene-7 alpha,12 alpha,24-triol (ND-1) and 3 alpha-(carboxymethyl)-5 beta-cholan-7 alpha,12 alpha,24-triol (ND-2). The derivative ND-1 has more hydrophobic convex surface than deoxycholic acid (D), but its partition coefficient in 1-octanol-aqueous phase is lower than one of ursodeoxycholic acid (UD), which means that ND-1 has smaller total hydrophobic surface in comparison to UD. The anion D shows greater increase in DPPC monolayer surface pressure than it can be derived from the size of its hydrophobic surface at the beta side of steroid skeleton. Membrane toxicity of ND-1 and ND-2 is lower than the one of D. The derivative ND-1 has lower value of the critical micellar concentration (cmc) than the anion D. At cmc ND-1 and ND-2 build Small primary micelles, while at the concentrations several times higher than cmc they form secondary micelles. The equilibrium constant of nitrazepane incorporation into the ND-1 and the ND-2 micelles implies that these micelles have larger hydrophobic nuclei than the micelles of natural dihydroxy bile acid derivative anions. (C) 2020 Elsevier B.V. All rights reserved.