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The aim of this study was to design co-loaded liposomes to achieve the synchronized delivery and release.Oxaliplatin and irinotecan hydrochloride, as one of recommended combination schemes for the treatment of colorectal cancer in clinic, were co-loaded into the liposomes.The molar ratio of the two drugs was set at 1∶1.5, which was in accordance with the dosage used in clinic.Oxaliplatin and irinotecan were assembled into the liposomes in sequence using ethanol injection method followed with ammonium sulfate gradient method, and the particle sizes of the co-loaded liposomes were less than 200 nm with uniform size distribution.The results of the In vitro release studies showed that the two drugs could be synchronously released from the co-loaded liposomes,which meant the optimized synergistic ratio of two drugs could be achieved.In vitro cellular uptake studies was carried out to evaluate the co-delivery ability of liposomes, the results revealed that co-loaded liposomes could efficiently deliver the two drugs into the same cells, indicating their potential as carriers for enhancing the cancer therapy efficiency.In vitro cytotoxicity evaluation demonstrated that the co-loaded liposomes exhibited higher cytotoxicity than the mixture of single loaded liposomes in both CT-26 and HCT-116 cells.Furthermore, the co-loaded liposomes also presented superior anti-tumor activity in CT-26 bearing BALB/c mice.In vivo safety assessment demonstrated that the co-loaded liposomes had lower toxicities than their solution formulations.These results indicated that oxaliplatin and irinotecan hydrochloride co-loaded liposomes would be an efficient formulation for improving colorectal cancer therapy with potential clinical applications.