Investigation of the effect of Ac2-26 loaded nanoparticles on intestinal wound and anastomosis healing during inflammatory processes in the gut

• Applicant: Privatdozent Dr. Philipp-Alexander Neumann
• Subject Area: General and Visceral Surgery
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403076667

Inflammatory bowel diseases (IBD) - comprising ulcerative colitis and Crohn´s disease - represent chronic inflammatory disorders of the gastrointestinal tract that are associated with relapsing symptoms of severe diarrhea, fever, weight loss, and abdominal pain. Immune suppressive medical therapy is considered the first line approach for treatment of IBD. However, although treatment options have markedly advanced during recent years, in their lifetime over 50% of patients with Crohn´s disease and about 30% of patients with ulcerative colitis still require surgical interventions. Depending on the type of operation and diagnosis, in most cases surgical resection of the diseased bowel is needed. Following resection, bowel continuity is restored by surgical suturing (anastomosis), which is followed by a process termed anastomotic healing. Undisturbed anastomotic healing is essential for the postoperative recovery of the patient and failed anastomotic healing is associated with considerable morbidity. Despite technical advancements in surgery, anastomotic leakage can still be detected in up to 30% of the cases following colorectal resections. Especially in the presence of severe systemic and/or local inflammation, such as in patients with IBD, anastomotic healing can be seriously impaired. In case of severe inflammation it is important to treat the source without inhibiting local healing processes, needed for anastomotic healing. Recently studies have investigated the effect of mediators that actively induce resolution from inflammation rather then merely inhibiting inflammation. One of these resolving mediators is Annexin A1 or its mimetic peptide Ac2-2 respectively. We have shown, that aplication of Annexin A1 inhibitis inflammation and induces wound healing during inflammatory processes in the gut. A possible way of targeted delivery of the mediator is through the use of nanoparticles. The aim of this proposal is to investigate oral and local delivery of Ac2-26 loaded nanoparticles for induction of anastomotic healing during colitis.

• DFG Programme: Research Grants