KaatDeClercq

Kaat De Clercqkaat

Laboratory of Pharmaceutical Technology

Ottergemsesteenweg 460
B-9000 Gent (Belgium)
Tel.: +32-9-264.83.55
E-mail:
Education: Pharmacist (Master in Drug Development)

 

Development of a gelling system for intraperitoneal administration with a dual activity : prevention of postsurgical peritoneal adhesions combined with a sustained release of paclitaxel for the local treatment of peritoneal carcinomatosis of ovarion origin

Peritoneal carcinomatosis (PC) is, in most cases, a secondary cancer originating from colorectal, gastric or ovarian cancer.  Ovarian cancer disseminates to the abdominal-pelvic cavity in a very early stage of the disease, peritoneal spread is diagnosed in the majority of ovarian cancer patients. PC is associated with poor prognosis and low quality of life. Current standard treatment is cytoreductive surgery in combination with (hyperthermic) intraperitoneal chemotherapy ((H)IPEC).  Local administration of chemotherapy instead of intravenous  chemotherapy has improved the mean overall survival of patients with advanced ovarian cancer. The rationale of intraperitoneal (IP) therapy is to maximize drug concentration within the abdominal cavity in order to increase drug penetration into the tumor cells, while minimizing systemic exposure to reduce side effects. The effectiveness of IP chemotherapy depends on uniform drug distribution throughout the peritoneal cavity. The formation of peritoneal adhesions is inevitable after cytoreductive surgery and hampers the effectiveness of IP chemotherapy. Furthermore, peritoneal adhesions are associated with severe complications including small bowel obstruction, female infertility and chronic abdominal pain. In addition, HIPEC is a very invasive technique for the patient, complications include anastomotic leaking and bowel perforation. Therefore, a biocompatible formulation that can simultaneously prevent peritoneal adhesion formation and improve IP chemotherapy by providing local drug release over a prolonged period is of high clinical interest.

The aim of this PhD project is the development of a formulation that can simultaneously improve IP chemotherapy and prevent postsurgical peritoneal adhesions. A gelling system will be developed and completely characterized in vitro and in vivo. The effectiveness of the formulation to prevent postsurgical peritoneal adhesions will be evaluated in a mouse model using the abraded peritoneal wall-cecum model. Paclitaxel will be incorporated in the formulation and drug release rate will be evaluated both in vitro and in vivo. The efficacy of the anti-cancer therapy will be investigated in a mouse model for peritoneal metastasis.