RELATIVE CONTRIBUTION OF PHOSPHATIDYLCHOLINE AND MONOGLYCERIDE TO ABSORPTION ENHANCEMENT OF LOW-MOLECULAR-WEIGHT HEPARIN (FRAGMIN) BY A NEW LIPID-BASED DRUG-DELIVERY SYSTEM IN MONOLAYERS OF HUMAN INTESTINAL EPITHELIAL CACO-2 CELLS AND AFTER RECTAL ADMINISTRATION TO RABBITS

The relative contribution of the constituents of a novel drug delivery system based on a lipid matrix to its absorption-enhancing properties was studied in monolayers of human intestinal epithelial Caco-2 cells and after rectal administration to New Zealand White rabbits. Chromatographically purified soybean phosphatidylcholine and medium chain monoacylglycerol were chosen as lipid matrix (PC:MG). Five different compositions of PC:MG ranging from pure MG through 1:3, 1:1 and 3:1 (w/w) mixtures to pure PC were investigated for their effects on cell toxicity, epithelial permeability and transport of low molecular weight heparin (Fragmin) and mannitol in Caco-2 monolayers. The results indicate that MG enhances and PC inhibits all of these effects in the monolayers. Similar results were obtained after rectal administration to New Zealand White rabbits, suggesting that the effects of PC:MG can be controlled in vivo by varying the relative proportions of MG and PC in the mixtures.