Intraperitoneal administration of PLGA nanoparticles could deliver the cargo to tumor-associated macrophages with less spreading peritoneal macrophages in the treatment of peritoneal carcinomatosis

Abstract

The survival time of patients with peritoneal metastasis is limited despite all treatments. Recent studies revealed that tumor-associated macrophages (TAMs) are educated in the tumor microenvironment for tumor growth and progression. The use of nanoparticles is considered an opportunity to deliver the therapeutics for depletion or re-education of these TAMs. In this study, it was planned to answer whether Poly(lactic-co-glycolic acid) (PLGA) nanoparticles applied to the peritoneum could be successful in delivering drugs to TAMs in peritoneal metastasis. For this purpose, Nile red loaded PLGA nanoparticles were prepared and characterized. Nil-PLGA NPs and nil red solution were injected intraperitoneally to mice model of CT-26 colon adenocarcinoma peritoneal metastasis, and nile red labeled macrophages were evaluated with the flow cytometer. The average particle size and zeta potential of nanoparticles were found as 238.4 +/- 22.9 nm and 1.38 +/- 1.35 mV, respectively. Labeled macrophages percent in the tumor was not found statistically different. On the other hand, after intraperitoneal administration of nil red solution, there was a very high nile red transfer to macrophages within the peritoneum. This widespread transfer was prevented by the application of nile red-loaded nanoparticles. This result shows that intraperitoneal application of PLGA nanoparticles could be an opportunity for drug delivery to TAMs with less damage to intraperitoneal macrophages.