Effective co-encapsulation of doxorubicin and irinotecan for synergistic therapy using liposomes prepared with triethylammonium sucrose octasulfate as drug trapping agent

Abstract

The combination regimen of irinotecan (IRI) and doxorubicin (DOX) for cancer treatment has been frequently exploited in clinical studies, but face challenges in design of efficacious combination drug delivery systems. Here we demonstrate a novel nanoliposome constructed by triethylammonium sucrose octasulfate gradient loading method for co-delivering the two therapeutic agents. In vitro cytotoxicity of IRI, DOX and their combinations against breast cancer cells (4T-1), non-small cell lung cancer cells (A549) and colon cancer cells (HT-29) was evaluated to screen optimal synergistic ratio of the two drugs. The co-delivery nanocarrier maintained the synergistic ratio in vivo, and increased tumor distribution of both drugs (≈2.18-fold vs single drug-loaded formulations). IRI/DOX co-loaded liposomes, with exceedingly high drug-to-phospholipid ratio of 0.61: 1 (molar ratio), exhibit potent antitumor efficacy in the 4T-1 mammary carcinoma xenograft, compared to the mixture of single drug-loaded liposomes (P < 0.001). This co-encapsulated and co-delivered nanoliposome technology offers a promising strategy for cancer treatment.

Keywords: Co-loaded liposome; Combination therapy; Doxorubicin; Drug delivery; Irinotecan.