Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

Intraperitoneal (IP) administration of nano-sized delivery vehicles containing small interfering RNA (siRNA) has recently gained attention as an alternative route for the efficient treatment of peritoneal carcinomatosis. The colloidal stability of nanomatter following IP administration has, however, not been thoroughly investigated yet. Here, enabled by advanced microscopy methods such as single particle tracking and fluorescence correlation spectroscopy, we follow the aggregation and cargo release of nano-scaled systems directly in peritoneal fluids from healthy mice and ascites fluid from a patient diagnosed with peritoneal carcinomatosis. The colloidal stability in the peritoneal fluids was systematically studied as a function of the charge (positive or negative) and poly(ethylene glycol) (PEG) degree of liposomes and polystyrene nanoparticles, and compared to human serum. Our data demonstrate strong aggregation of cationic and anionic nanoparticles in the peritoneal fluids, while only slight aggregation was observed for the PEGylated ones. PEGylated liposomes, however, lead to a fast and premature release of siRNA cargo in the peritoneal fluids. Based on our observations, we reflect on how to tailor improved delivery systems for IP therapy.