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

Publication date: Available online 29 December 2018Source: International Journal of PharmaceuticsAuthor(s): Jieru Liu, Dongxu Chi, Siyan Pan, Liwen Zhao, Xue Wang, Dun Wang, Yongjun WangAbstractThe 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.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research