Oral administration of insulin included in fine W/O/W emulsions to rats

Fine W/O/W emulsions having controlled median diameters between 0.7 and 30 μm were prepared using octanoic acid triacylglycerol (C8:0TG) and soybean oil as the oil phases. Transport enhancement of a model hydrophilic compound by the soybean-oil hydrolysates was investigated using Caco-2 model intestinal epithelial cells. The results were compared with those from in vivo experiments; in which rats were administered various types of W/O/W emulsions encapsulating insulin. Transport enhancement effect of the emulsions was evaluated by the blood-sugar level collected from the coccygeal vein. The pancreatic lipase-catalyzed hydrolysates of soybean oil showed high transport enhancement effects in Caco-2 model system, but the administration of insulin included in the W/O/W emulsion prepared with soybean oil had no hypoglycemic effect on rats. The transport enhancement effect of the hydrolysates of soybean oil in Caco-2 model system was attenuated by the coexistence of a coating material used in spray-drying process or triacylglycerol. On the other hand, administration of the W/O/W emulsions prepared with C8:0TG and encapsulating insulin showed a hypoglycemic effect on rats. Administration of the W/O/W emulsion having an oil-droplet median diameter of 2.3 μm also showed the hypoglycemic effect in the earlier period than that of the coarse W/O/W emulsion having a diameter of 38 μm. However, the emulsion with the diameter of 0.7 μm exhibited no effect. These results suggested that the transport enhancement effect of the W/O/W emulsion prepared with C8:0TG depended on the size of the oil droplets, while too fine an emulsion had no such effect.