Development of a rat capnoperitoneum phantom to study drug aerosol deposition in the context of anticancer research on peritoneal carcinomatosis

Abstract

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a promising approach with a high optimization potential for the treatment of peritoneal carcinomatosis. To study the efficacy of PIPAC and drugs, first rodent cancer models were developed. But inefficient drug aerosol supply and knowledge gaps concerning spatial drug distribution can limit the results based on such models. To study drug aerosol supply/deposition, computed tomography scans of a rat capnoperitoneum were used to deduce a virtual and a physical phantom of the rat capnoperitoneum (RCP). RCP qualification was performed for a specific PIPAC method, where the capnoperitoneum is continuously purged by the drug aerosol. In this context, also in-silico analyses by computational fluid dynamic modelling were conducted on the virtual RCP. The physical RCP was used for ex-vivo granulometric analyses concerning drug deposition. Results of RCP qualification show that aerosol deposition in a continuous purged rat capnoperitoneum depends strongly on the position of the inlet and outlet port. Moreover, it could be shown that the droplet size and charge condition of the drug aerosol define the deposition efficiency. In summary, the developed virtual and physical RCP enables detailed in-silico and ex-vivo analyses on drug supply/deposition in rodents.

Performance of different nebulizers in clinical use for Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

“…It is therefore recommended that nozzles for which the technical/granulometric characteristics differ from the current standard technology must be subjected to preclinical proof of equivalence in terms of spatial drug distribution, tissue penetration and concentration before routine clinical use. It is expected that representative in-silico models like the ones used in [ 36 , 37 ] will be available in the near future. New nebulizers should be investigated and introduced for clinical use in accordance with the IDEAL-D framework.…”

Development and technical validation of an ultrasound nebulizer to deliver intraperitoneal pressurized aerosols in a rat colon cancer peritoneal metastases model

“…At that pressure the spatial geometry and the volume of the rat capnoperitoneum was determined by means of breathing-triggered computer tomography volumetry (Micro-CT SkyScan 1278, Bruker, Billeric, USA) in five healthy male Wistar rats (Charles River, France) of 250 to 350 g body weight. A median volume of the rat capnoperitonea at a pressure of 8 to 10 mmHg of 130 ml ± 10 ml was observed [ 14 ]. Based on these data, we designed artificial rat capnoperitonea phantoms by using cylindrical polyethylene terephthalate cans that were internally coated with a 1 to 2 mm thick agar layer and had an approximately similar geometry dimension of 4.0 × 10.5 cm as the in-vivo rat capnoperitoneum.…”