Transport of steroids at model biomembrane surfaces and across organic liquid-aqueous phase interfaces

Phospholipid vesicles (liposomes) have been widely studied for their potential applications in controlled drug delivery. In one example, proposed for transdermal utilization, drug-loaded liposomes are dispersed as discrete entities within an aqueous gel matrix which can then be applied to the skin. Preliminary studies indicated that the zero-order release of a model steroid (progesterone), from the prototypal delivery system into aqueous solution, was controlled by slow transport of drug at the liposome bilayer-aqueous gel interface. To investigate this behavior further, the present investigation extends the observations to four steroids spanning a range of physicochemical properties. Additionally, the transport kinetics at the model biomembrane surfaces within the delivery system have been compared to the corresponding rates of interfacial transfer at simple organic liquid-aqueous solution boundaries. The mass-transfer kinetics in both systems are sensitive to the lipophilicity of the steroid and the degree to which the solute can interact with the interfacial region. Not unexpectedly, transport at the model biomembrane surface is slower than that across the simple liquid-liquid interface. However, the magnitude of the difference in kinetics (10⁶ cm/s) is substantial and reflects considerable structuring close to the membrane headgroup region. It is hypothesized that the combination of (a) high lipid acyl chain microviscosity, (b) strong headgroup interactions, and (c) ordered water structure on the aqueous side of the interface provides a well-constructed edifice and barrier that very effectively controls the "escape" of lipophilic solutes from biological membranes.