High pressure intraperitoneal aerosolization of chemotherapeutics, nanoparticles and hydrogels to treat peritoneal carcinomatosis: effect on tumor penetration, biodistribution and anti-cancer activity.

01 January 2019 → 31 December 2022
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Morphological sciences not elsewhere classified
Project description

Yearly, about 150000 people develop peritoneal carcinomatosis (PC) in Europe alone. PC is
characterized by the spread of numerous small tumor nodules in the peritoneal cavity. After initial
surgery, where as many tumor nodules are removed as possible, the patients receive the
intraperitoneal injection of chemotherapeutics such as cisplatin. The prognosis of this patients is
however poor, with a median survival of 8 to 12 months. Problems are the limited retention of the
chemotherapeutics in the peritoneal cavity and the poor tumor penetration. Currently, the
nebulization of an aerosol of chemotherapeutics in the peritoneal cavity under high pressure is
evaluated to enhance tumor penetration and to ensure an optimal spreading over the whole
peritoneal surface. It is not clear, however, to which extent nebulization is preferred over injection
of a solution and whether or not advanced pharmaceutical formulations suchs as nanoparticles and
controlled release delivery systems can withstand the high pressure during nebulization. We will
develop an ex vivo model to test nebulization of chemotherapeutics, nanoparticles and hydrogels on
isolated peritoneal tissue. Also, the effect of electrostatic nebulization will be evaluated on charged
particles such as non-viral gene delivery complexes. Furthermore, we will compare tumor
penetration and biodistribution in a rat model of peritoneal carcinomatosis to systematically study
the effect of nebulization versus injection in vivo.