Lipid nanoparticles (LNPs) or liposomes are the most widely used drug carriers for nanomedicines. The size of LNPs is one of the essential factors affecting drug delivery efficiency and therapeutic efficiency. Here, we demonstrated the effect of lipid concentration and mixing performance on the LNP size using microfluidic devices with the aim of understanding the LNP formation mechanism and controlling the LNP size precisely. We fabricated microfluidic devices with different depths, 11 μm and 31 μm, of their chaotic micromixer structures. According to the LNP formation behavior results, by using a low concentration of the lipid solution and the microfluidic device equipped with the 31 μm chaotic mixer structures, we were able to produce the smallest-sized LNPs yet with a narrow particle size distribution. We also evaluated the mixing rate of the microfluidic devices using a laser scanning confocal microscopy and we estimated the critical ethanol concentration for controlling the LNP size. The critical ethanol concentration range was estimated to be 60–80% ethanol. Ten nanometer-sized tuning of LNPs was achieved for the optimum residence time at the critical concentration using the microfluidic devices with chaotic mixer structures. The residence times at the critical concentration necessary to control the LNP size were 10, 15–25, and 50 ms time-scales for 30, 40, and 50 nm-sized LNPs, respectively. Finally, we proposed the LNP formation mechanism based on the determined LNP formation behavior and the critical ethanol concentration. The precise size-controlled LNPs produced by the microfluidic devices are expected to become carriers for next generation nanomedicines and they will lead to new and effective approaches for cancer treatment.

We conducted a molecular biological investigation to determine the outcomes of hyperthermic intraperitoneal chemotherapy (HIPEC) treatment, and whether it is effective in all cases for patients with peritoneal dissemination of colon cancer. In the HIPEC group, the 3-year survival rate was 39.2%, whereas in the non-HIPEC group the 3-year survival rate was 15.6%. MUC2 expression was investigated in the HIPEC group, in patients positive for MUC2 expression, and the 3-year survival rate was 0.0%, while in patients negative for MUC2 expression, the 3-year survival rate was 61.1%. In addition, as a result of introducing MUC2-siRNA into a colon cancer cell line with high expression of the MUC2 gene, the cell death rate from heat and anticancer agents increased 40% in comparison with colon cancer cells in which scrambled siRNA had not been introduced. HIPEC therapy is thought to be effective in prolonging survival in patients with peritoneal dissemination of colon cancer, and MUC2 expression is thought to be useful as an indicator to assess its effectiveness in colon cancer cells.

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