The effect of a drug-delivery system consisting of soybean phosphatidyl choline and medium-chain monoacylglycerol on the intestinal permeability of hexarelin in the rat

The aim of this study was to investigate if the effective in-situ permeabil ity (P-eff) of a new growth hormone-releasing peptide, hexarelin, along rat intestine was enhanced by a lipid matrix drug-delivery system comprising a mixture of soybean phosphatidyl choline and medium-chain monoacylglycerol (PC-MG). The study was performed with and without a protease inhibitor, Pef abloc SC. To enable better understanding of the mechanism of action of this delivery system we also studied the uptake of a small hydrophilic molecule , atenolol. PC-MG at a concentration of 15 mmol L-1 increased the jejunal P-eff of hexa relin approximately 20-fold, both in the presence and absence of Pefabloc S C, whereas P-eff was not increased in the ileum and colon. PC-MG had no eff ect on the jejunal, ileal and colonic P-eff of atenolol. Complete recovery of the non-absorbable molecule PEG 4000 showed that functional intestinal v iability was maintained in all experiments. Although the results obtained in this study are promising, pharmacokinetic and toxicological studies are required to investigate if this delivery syst em is a suitable and safe candidate for improving the oral bioavailability of hexarelin.