De. Decker et al., KINETICS AND THERMODYNAMICS OF EMULSION DELIVERY OF LIPOPHILIC ANTIOXIDANTS TO CELLS IN CULTURE, Chemistry and physics of lipids, 76(1), 1995, pp. 7-25
Oil-in-water emulsions are being used increasingly for the delivery of
lipophilic drugs, but the fundamental physicochemical principles gove
rning such delivery have not been explored. We determined the kinetics
and thermodynamics of delivery from emulsions to cells in culture for
two lipophilic compounds, U74006 and U74500. Two fundamental properti
es dominate the delivery, (a) the concentration of the compound in the
lipid phase of the emulsion is directly proportional to the concentra
tion of the compound in cells at equilibrium, and (b) the rate of tran
sfer is directly proportional to the concentration of particles in con
tact with the cells. Thus, the transfer is consistent with direct part
itioning from the lipid phase of the emulsion to cells and occurs by t
he direct collision of emulsion particles with cells. The details of t
he mechanism of delivery differ between the two compounds. Specificall
y, delivery of U74006 is first-order with respect to the drug accumula
ting in the cells. The transfer of U74500 is best described as a sum o
f two simultaneous pseudo first-order processes consistent with delive
ry from a single donor compartment to two receiver compartments. Furth
ermore, two molecules of U74500 appear to be involved in each transfer
event. Our results show that relatively simple principles govern the
delivery of compounds from oil-in-water emulsions to cells.