Prevention of adhesions post-abdominal surgery: Assessing the safety and efficacy of Chitogel with Deferiprone in a rat model

Abstract

Introduction Adhesions are often considered to be an inevitable consequence of abdominal and pelvic surgery, jeopardizing the medium and long-term success of these procedures. Numerous strategies have been tested to reduce adhesion formation, however, to date, no surgical or medical therapeutic approaches have been successful in its prevention. This study demonstrates the safety and efficacy of Chitogel with Deferiprone and/or antibacterial Gallium Protoporphyrin in different concentrations in preventing adhesion formation after abdominal surgery. Materials and methods 112 adult (8–10 week old) male Wistar albino rats were subjected to midline laparotomy and caecal abrasion, with 48 rats having an additional enterotomy and suturing. Kaolin (0.005g/ml) was applied to further accelerate adhesion formation. The abrasion model rats were randomized to receive saline, Chitogel, or Chitogel plus Deferiprone (5, 10 or 20 mM), together with Gallium Protoporphyrin (250μg/mL). The abrasion with enterotomy rats were randomised to receive saline, Chitogel or Chitogel with Deferiprone (1 or 5 mM). At day 21, rats were euthanised, and adhesions graded macroscopically and microscopically; the tensile strength of the repaired caecum was determined by an investigator blinded to the treatment groups. Results Chitogel with Deferiprone 5 mM significantly reduced adhesion formation (p<0.01) when pathologically assessed in a rat abrasion model. Chitogel with Deferiprone 5 mM and 1 mM also significantly reduced adhesions (p<0.05) after abrasion with enterotomy. Def-Chitogel 1mM treatment did not weaken the enterotomy site with treated sites having significantly better tensile strength compared to control saline treated enterotomy rats. Conclusions Chitogel with Deferiprone 1 mM constitutes an effective preventative anti-adhesion barrier after abdominal surgery in a rat model. Moreover, this therapeutic combination of agents is safe and does not weaken the healing of the sutured enterotomy site.

Wound healing in endoscopic sinus surgery: Phase 1 clinical trial evaluating the role of Chitogel with adjuvants

“…16,22 Although both of these agents were shown to have good safety and tolerability profiles, little additional benefit was seen in ostial preservation. A larger sample size is needed to comprehensively assess possible benefits with lower doses used in subsequent studies with good effect 26,27 in terms of preservation of ostial size, mucosal healing and antibacterial effects.…”

Effects of stem cells and amniotic fluid on uterus and ovaries in a rat model of abdominal adhesions: a controlled study

“…Studies to prevent intra-abdominal adhesions after surgery have been ongoing since the beginning of the last century ( 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ). Considering the significant postoperative complications caused by adhesions, such as second surgery, ileus, pain, intraoperative complications in further surgeries, and infertility, initiating an effective treatment is clinically available ( 1 ).…”

“…In a study by Canbaz et al ( 18 ) in a rat model, gonadotropin-releasing hormone agonist therapy successfully reduced postoperative adhesion formation but was not superior to intraperitoneal Ringer’s lactate solution. An increasing number of studies ( 19 ) have researched the adhesion prevention capability of various barrier agents ( 20 , 21 , 22 , 23 ), various combination gels ( 24 , 25 , 26 , 27 , 28 , 29 ), biomaterials ( 30 ), growth factor inhibitors ( 31 , 32 ), and stem cells ( 33 , 34 , 35 ), which is evidence of the importance of adhesion-related problems.…”

Development of Gallium(III) as an Antimicrobial Drug Targeting Pathophysiologic Iron Metabolism of Human Pathogens

“…91,101 When used with Chitogel and Deferiprone, GaPP significantly inhibited adhesion and biofilm formation of microbial infections post-abdominal surgery. 163,173 In 2021, Qiao et al investigated a copolymer constructed with amphiphilic deferoxamine and gallium conjugated to a xenosiderophore (pGQ-DG). 157 They tested the copolymer in a murine wound-healing model using female BALB/c mice with 0.8 cm radius circular skin wounds infected with P. aeruginosa.…”

“…Gallium has been shown to be an effective topical treatment especially when incorporated into scaffolding matrices such as chitogel. , Topical treatment led to a significant increase in clearance of S. aureus biofilms in sinusitis model. Additionally, plasma levels of GaPP were monitored over the course of the 7-day treatment, and at no point did concentrations reach detectable levels.…”