MECHANISM OF PROMOTION OF LYMPHATIC DRUG ABSORPTION BY MILK-FAT GLOBULE-MEMBRANE

A soybean oil emulsion containing vitamin D-3, which was prepared usin g MFGM as an emulsifier, was administered to rats. The percentage of v itamin D-3 recovered in lymph over 12 h was 19.2%. This was reduced to 2.05% when rats were treated with colchicine, a chylomicron synthesis inhibitor, and further to only 0.27% when pancreatic ducts were ligat ed. When each of these MFGM micro-dispersions (micro-emulsions or mixe d micelles of 40-150 nm diameter), i.e., without taurocholate (TC) or pancreatic lipase (PL); with TC alone; and with both TC and FL, was ad ministered to pancreatic duct-ligated rats, the recovered percentages of vitamin D-3 in lymph were 3.45, 10.6 and 20.4%, respectively. These results suggest that pancreatic lipases and bile salts are critical f actors for the absorption of vitamin D-3 in MFGM dosage forms and the promotive effect of MFGM takes place in the lumen of the intestine rat her than the epithelial cells of the intestine. The particle morpholog y and physical characteristics of MFGM micro-dispersion were also anal yzed by electron microscopy and electron spin resonance (ESR) spectros copy. The results suggest that the micro-dispersion was a mixed micell e when TC was present, and as an emulsion when TC was absent. Furtherm ore, although the size and form of the mixed micelles with and without PL were very similar, the membrane fluidity evaluated from the ESR ex periment for the micelles with PL was higher than that for the micelle s without FL. This suggests that PL plays an important role in modifyi ng micelle characteristics. It is concluded that mixed micelle formati on by MFGM and bile salts in the lumen is a dominant mechanism of prom otion of lymphatic drug absorption by MFGM.