title: Genipin-crosslinked gelatin microspheres as a strategy to prevent postsurgical peritoneal adhesions: In vitro and in vivo characterization.
abstract: Peritoneal adhesions are a common complication after abdominal surgery. They cause small bowel obstruction, female infertility and chronic abdominal pain. Peritoneal adhesions also hamper uniform drug distribution in the peritoneal cavity, thereby reducing the efficacy of intraperitoneal chemotherapy after cytoreductive surgery.
  
  
  
  The goal of this study was to develop a formulation that prevents peritoneal adhesions, evenly distributes in the abdominal cavity, and simultaneously extends residence time and improves local drug concentration. This report describes the formulation and characterization of genipin-crosslinked gelatin microspheres (GP-MS).
  
  
  
  Spheroid gelatin microspheres were prepared by an emulsification solvent extraction method. A higher degree of crosslinking was obtained by increasing genipin concentration and crosslinking time. The degree of crosslinking allowed to tailor the degradation rate of GP-MS, hence their residence time. GP-MS did not affect cell viability. In vivo experiments showed excellent GP-MS biocompatibility and degradation characteristics. GP-MS were distributed evenly throughout the abdominal cavity. Adhesions were induced in Balb/c mice by application of an abraded peritoneal wall-cecum model. GP-MS-treated mice developed significantly less postsurgical adhesions compared to saline and Hyalobarrier(®) group. Histopathological examination showed a decrease of peritoneal inflammation over time in GP-MS-treated mice with complete recovery of peritoneal wounds post-operative day 14.
  
  
  
  GP-MS are a promising strategy to prevent postoperative peritoneal adhesions and improve efficacy of postoperative intraperitoneal chemotherapy.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: Kaat
authors.initials: K
authors.lastname: De Clercq
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Schelfhout
authors.affiliation: Laboratory of Experimental Cancer Research, Ghent University, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.affiliation: Laboratory of Experimental Cancer Research, Ghent University, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Department of Pathology, Ghent University Hospital, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Bockstal
authors.affiliation: Department of Surgery, Ghent University Hospital, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Ceelen
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium. Electronic address: chris.vervaet@ugent.be.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D034841:Abdominal Cavity / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004195:Disease Models, Animal; D004655:Emulsions / Q000737:chemistry; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D039823:Iridoids / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010537:Peritoneum / Q000473:pathology*; D011183:Postoperative Complications / Q000473:pathology* / Q000517:prevention & control*; D013501:Surface-Active Agents / Q000737:chemistry; D000267:Tissue Adhesions / Q000209:etiology / Q000473:pathology / Q000517:prevention & control
chemical_list: D003432:Cross-Linking Reagents; D004655:Emulsions; D039823:Iridoids; D013501:Surface-Active Agents; D005780:Gelatin; C007834:genipin
keywords: Anti-adhesion barrier; Crosslinking; Genipin; Microspheres; Peritoneal adhesions prevention; Post-operative adhesions