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


Celebi N., Turkyilmaz A., Gonul B., Ozogul C.

JOURNAL OF CONTROLLED RELEASE, vol.83, no.2, pp.197-210, 2002 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 83 Issue: 2
  • Publication Date: 2002
  • Doi Number: 10.1016/s0168-3659(02)00198-0
  • Journal Name: JOURNAL OF CONTROLLED RELEASE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.197-210
  • Keywords: epidermal growth factor, microemulsion, acute gastric ulcer, ulcer score, histological evaluation, SYNTHETIC HUMAN UROGASTRONE, DNA-SYNTHESIS, PROSTAGLANDINS, CYTOPROTECTION, CYCLOSPORINE, ABSORPTION, INJURY, MUCOSA
  • Gazi University Affiliated: No

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 degreesC). EGF was administered at a dose of 6 mug/kg per day intraperitoneally and intraperitoneally for 7 days. Basal gastric acid secretion (muequiv. H+/30 min), ulcer score (mm(2)) and tissue mucus levels (mug/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). (C) 2002 Elsevier Science B.V. All rights reserved.