Partitioning of some 21-alkyl esters of hydrocortisone and cortisone

Abstract

The temperature dependency of the partitioning of some steroids has been determined between dimyristoyl phosphatidylcholine liposomes; isopropyl myristate and 0.9% saline (0.15 M). Partition coefficients increased as a function of temperature below the endothermic phase transition temperature (T c) of the phospholipid, but decreased above this temperature. The IPM-saline partition coefficients of the esters of hydrocortisone and cortisone decreased as a function of temperature. Free energies (ΔG w→1) for all steroids studied were negative. The transfer process was found to be entropy-dominated in both cases. Partitioning into liposomes occurs into areas slightly more hydrophilic than n-octanol and IPM. Ketones substituted on the 11-position of 21-OH steroids have greater hydrogen-bonding capability than 11-OH compounds. Esterification of the 21-hydroxyl leads to an increase in partitioning, because of a positive entropie effect and in spite of a large positive enthalpic effect. This opposing enthalpic effect is due to the increased difficulty in inserting the steroid acetate into a bilayer, due to its increased dimensions relative to the parent steroid. The negative free energy effect of steroidal side-chain lengthening per −CH 2−: group is higher than those reported for methylene group contribution of other solutes in DMPC liposome partitioning systems.