Experimental evaluation of icodextrin delivery as pressurized aerosol (PIPAC): Antiadhesive and cytotoxic effects

Abstract

Background: Icodextrin (IDX) is an antiadhesive polymer that can be used as a carrier solution for intraperitoneal (IP) delivery of chemotherapeutic drugs.

Methods: We investigated the suitability of IDX solution as a carrier of Cisplatin and Doxorubicin for delivery as pressurized intraperitoneal aerosol chemotherapy (PIPAC). We examined the sprayability of IDX, the aerosol characteristics, the stability of the molecule after aerosolization, the effects of IDX on the adhesion of MKN45 human gastric cancer cells, the synergistic effect of aerosolized IDX with Cisplatin and Doxorubicin, and the chemical stability of IDX, Cisplatin, and Doxorubicin in combination.

Results: Delivery of IDX as PIPAC is feasible with no particular restrictions. The median droplet size of 35.7 μm did not change at increasing concentrations. IDX withstood the shear forces applied by the nebulizer and remained stable after aerosolization (ANOVA, p = 0.97). IDX did not impair the cytotoxic effects of Cisplatin and Doxorubicin (ns). IDX had a significant antiadhesive impact alone (p < 0.03) and in combination with Cisplatin and Doxorubicin (p < 0.02). IDX as a carrier for Cisplatin and Doxorubicin remained stable at 4 °C for three months and did not cause degradation of those two substances.

Conclusion: The proposed combination takes advantage of the antiadhesive properties of IDX, the cytotoxic effect of Cisplatin and Doxorubicin, and an advanced drug delivery system.

Keywords: Adhesions; Cancer; Cisplatin; Doxorubicin; Icodextrin; Intraperitoneal chemotherapy; PIPAC; Pressurized IntraPeritoneal aerosol chemotherapy.