Effects of epidermal growth factor microemulsion formulation on the healing of stress-induced gastric ulcers in rats

Abstract

The effects of intragastric (i.g.) administration of microemulsion formulation of epidermal growth factor (EGF) on the healing of acute gastric ulcers induced by cold-restraint stress in rats was studied and compared with intraperitoneal (i.p.) administration of solutions. In the microemulsion formulation (W/O), labrafil M 1944 CS was the oil phase. Arlacel 186 and Brij 35 were used as the surfactants. Absolute alcohol and distilled water were used as the co-surfactant and the aqueous phase, respectively. Acute gastric lesions were induced by cold-restraint stress for 4 h in the refrigerator (4.0+/-0.5 degrees C). EGF was administered at a dose of 6 microg/kg per day intraperitoneally and intraperitoneally for 7 days. Basal gastric acid secretion (microequiv. H+/30 min), ulcer score (mm(2)) and tissue mucus levels (microg/g tissue) were measured. Basal gastric secretion was significantly reduced after the administration of EGF microemulsion (ME+EGF) (P<0.05). There was no significant decrease in basal gastric acid secretion following i.p (IPEGF) and i.g (IG-EGF) of EGF administrations of solutions compared to their control groups (P>0.05). The results indicate that the highest reduction in the basal acid secretion was seen after the administration of a microemulsion of EGF formulation. The mean ulcer score was reduced by i.g treatment with the microemulsion dosage form of EGF in 7 days from 15.9+/-1.4 to 1.16+/-0.45 mm(2) and was almost completely healed in four of the animals. The results demonstrate that the ulcer score was significantly reduced in i.p. (IPEGF) solution (P<0.005), i.g (IG-EGF) solution (P<0.01) and i.g. microemulsion (ME+EGF) (P<0.01) treated groups compared to untreated group. In IG-EGF, ME+EGF treated groups, mucus levels increased significantly compared to their control groups(P<0.05 and P<0.01). In contrast, there was no significant change in the mucus levels following i.p. EGF administration (P>0.05).