rhEGF-containing thermosensitive and mucoadhesive polymeric sol-gel for endoscopic treatment of gastric ulcer and bleeding.
Gastrointestinal endoscopy is a standard diagnostic tool for gastrointestinal ulcers and cancer. In this study, we have developed recombinant human epidermal growth factor-containing ulcer-coating polymeric sol-gel for endoscopic application. Chitosan and pluronic F127 were employed for their thermoresponsive and bioadhesive properties. At temperatures below 21, polymeric sol-gel remains liquid during endoscopic application and transforms to gel at body temperature after application on ulcers. In an in vitro cellular wounding assay, recombinant human epidermal growth factor sol-gel significantly enhanced the cell migration and decreased the wounding area (68%) compared to nontreated, recombinant human epidermal growth factor solution, and sol-gel without recombinant human epidermal growth factor (42, 49, and 32 % decreased at day 1). The in vivo ulcer-healing study was performed in an acetic acid-induced gastric ulcer rat model and proved that our recombinant human epidermal growth factor endoscopic sol-gel facilitated the ulcer-healing process more efficiently than the other treatments. Ulcer sizes in the recombinant human epidermal growth factor sol-gel group were decreased 2.9- and 2.1-fold compared with those in the nontreated group on days 1 and 3 after ulceration, respectively. The mucosal thickness in the recombinant human epidermal growth factor sol-gel group was significantly increased compared to that in the nontreated group (3.2- and 6.9-fold on days 1 and 3 after ulceration, respectively). In a gastric retention study, recombinant human epidermal growth factor sol-gel stayed on the gastric mucosa more than 2 h after application. The present study suggests that recombinant human epidermal growth factor sol-gel is a prospective candidate for treating gastric ulcers via endoscopic application.
1Utah-Inha DDS and Advanced Therapeutics Research Center, Incheon, Korea.
Jin Hee
JH
Maeng
Jung Won
JW
So
Jungju
J
Kim
In Ae
IA
Kim
Ji Hoon
JH
Jung
Kyunghyun
K
Min
Don Haeng
DH
Lee
Su-Geun
SG
Yang
D002460:Cell Line; D004724:Endoscopy; D004815:Epidermal Growth Factor / Q000627:therapeutic use*; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy / Q000601:surgery*; D005782:Gels; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000188:drug therapy / Q000601:surgery*
D005782:Gels; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor
Gastric ulcer and bleeding; chitosan; endoscopic treatment; pluronic F127; rhEGF; thermosensitive sol–gel