Pp. Constantinides et al., ENHANCED INTESTINAL-ABSORPTION OF AN RGD PEPTIDE FROM WATER-IN-OIL MICROEMULSIONS OF DIFFERENT COMPOSITION AND PARTICLE-SIZE, Journal of controlled release, 34(2), 1995, pp. 109-116
The fibrinogen receptor antagonist SK and F 106760 is a water-soluble
tetrapeptide (M(r) 634) with very low oil/water partitioning and membr
ane permeability. Thus, the intraduodenal bioavailability of this pept
ide in the rat from a saline formulation was found to be less than 1%.
Upon formulation, however, in w/o microemulsions of different composi
tion and particle size, the intraduodenal bioavailability of SK and F
106760 was increased up to 29% depending on the microemulsion composit
ion. There was no apparent correlation between the particle size of mi
croemulsions (mean droplet diameter of 0.010-1.0 mu m) and enhanced ab
sorption. None of the investigated microemulsions induced gross change
s in gastrointestinal mucosa at a dosing volume of 3.3 ml/kg. Lipids c
ontaining medium-chain fatty acids play a major role on the observed a
bsorption enhancement. These findings further support the use of micro
emulsion formulations for oral drug/peptide delivery, provided however
, that development issues with these systems are properly addressed.