Effect of oxyethylene moiety in polyoxyethylene sorbitan esters on the pharmacokinetics of menatetrenone incorporated in O/W lipid emulsions prepared with polyoxyethylene sorbitan esters and soybean oil in rats

Abstract

Oil-in-water (O/W) lipid emulsions are suitable drug carriers for lipophilic drugs; however, the effects of numbers or chains of oxyethylene units within a surfactant molecule such as polyoxyethylene sorbitan esters (PSs) on the biological fate of these lipid emulsions have not yet been clarified. In this study, a series of PSs and soybean oil (SO) were utilized to prepare menatetrenone-incorporated lipid emulsions (SO/PSs), and the biological fate of menatetrenone administered as SO/PSs was studied at a clinical injection volume (0.1 mL kg−1) in rats. The plasma concentration and organ uptake of menatetrenone administered as SO/20OE-PSs (PSs with 20 oxyethylene units) was similar to that of SO/egg-yolk phosphatides (SO/EYP). The plasma concentration of menatetrenone was extensively lower for SO/6OE-PSs (PSs with 6 oxyethylene units) and SO/20OE-3FA-PSs (PSs with 20 oxyethylene units and 3 fatty acid chains) than that for SO/EYP, and menatetrenone uptake by the liver and spleen was higher for SO/6OE-PSs and SO/20OE-3FA-PSs, respectively, than those for SO/EYP. Furthermore, menatetrenone uptake by the lungs was also increased for SO/6OE-PS and SO/20OE-3FA-PS with double bonds in the fatty acid moieties of the PSs. These findings suggested that shortening the oxyethylene units or decreasing the oxyethylene chain numbers of emulsifiers resulted in a rapid clearance of the lipid emulsions from the circulation by extensive uptake via the liver, spleen or lungs.