Kinetics and thermodynamics of emulsion delivery of lipophilic antioxidants to cells in culture.
Oil-in-water emulsions are being used increasingly for the delivery of lipophilic drugs, but the fundamental physicochemical principles governing 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 properties dominate the delivery, (a) the concentration of the compound in the lipid phase of the emulsion is directly proportional to the concentration of the compound in cells at equilibrium, and (b) the rate of transfer is directly proportional to the concentration of particles in contact with the cells. Thus, the transfer is consistent with direct partitioning from the lipid phase of the emulsion to cells and occurs by the direct collision of emulsion particles with cells. The details of the mechanism of delivery differ between the two compounds. Specifically, delivery of U74006 is first-order with respect to the drug accumulating in the cells. The transfer of U74500 is best described as a sum of two simultaneous pseudo first-order processes consistent with delivery from a single donor compartment to two receiver compartments. Furthermore, 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.
Decker
D E
DE
Upjohn Laboratories, Cell Biology and Inflammation Research, Kalamazoo MI 49001, USA.
Vroegop
S M
SM
Goodman
T G
TG
Peterson
T
T
Buxser
S E
SE
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004655:Emulsions; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D011281:Pregnatrienes / Q000378:metabolism*; D051381:Rats; D013816:Thermodynamics; D014304:Triolein / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D004655:Emulsions; D010713:Phosphatidylcholines; D011281:Pregnatrienes; D014304:Triolein; C053356:U 74500A; C053355:tirilazad