Impacts of Intralipid on Nanodrug Abraxane Therapy and on the Innate Immune System

Abstract

A major obstacle to nanodrugs-mediated cancer therapy is their rapid uptake by the reticuloendothelial system that decreases the systemic exposure of the nanodrugs to tumors and also increases toxicities. intralipid has been shown to reduce nano-oxaliplatin-mediated toxicity while improving bioavailability. Here, we have found that Intralipid reduces the cytotoxicity of paclitaxel for human monocytic cells, but not for breast, lung, or pancreatic cancer cells. Intralipid also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. Using a xenograft breast cancer mouse model, we have found that Intralipid pre-treatment significantly increases the amount of paclitaxel reaching the tumor and promotes tumor apoptosis. the combination of intralipid with half the standard clinical dose of Abraxane reduces the tumor growth rate as effectively as the standard clinical dose. Our findings suggest that pre-treatment of intralipid has the potential to be a powerful agent to enhance the tumor cytotoxic effects of Abraxane and to reduce its off-target toxicities.

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“…Consequently, Intralipid has been found to improve bioavailability and reduce cytotoxicity in monocytic cells. In addition, a combination of Intralipid and Abraxane has been identified to reduce tumor growth significantly (38). In recent years, polymer-based drug delivery systems have been studied for drug delivery and ensuring the controlled release of anticancer agents with consistent doses over long periods.…”

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