Pharmacokinetics and Anti-Cancer Activity of Curcumin- and Pluronic P85-Loaded Mesoporous Silica Nanoparticles

This study aimed to investigate the pharmacokinetics of curcumin (CUR) and its anti-cancer activity against B16F10 cell in mice using CUR-and pluronic P85 (PP85)-loaded mesoporous silica nanoparticles.CUR was incorporated into mesoporous nanosilicate (SMB7) using a solvent extraction method, and PP85 was also loaded into SMB7 using a freeze-drying method.The final formulation, CUR-PP85-SMB7, was optimized at a ratio of 1:2:4 (w/w).The solubility and release profile of CUR from CUR-PP85-SMB7 were greatly improved compared with CUR alone.The plasma concentrations of CUR were also increased in mice administered CUR-PP85-SMB7 intraperitonially at a dose of 5 mg CUR compared with equivalent dose of standalone CUR.Moreover, tumor growth was inhibited through the repeated intraperitonial administration of CUR-PP85-SMB7 (20 mg CUR equivalent/kg for 7 days) in B16F10 melanoma-bearing mice, and the inhibition was even more marked than that of the CUR-SMB7 group with equivalent dose and the same dose in the CUR-only treatment group.The CUR concentration in tumor tissues at 4 h after the last CUR dose was the highest in the CUR-PP85-SMB7 group, and comparable in the CUR-SMB7 and CUR-only groups.These findings suggest that the P-glycoprotein (P-gp) inhibitory effect of PP85 from CUR-PP85-SMB7 can increase the CUR accumulation in B16F10 melanoma tissues and improved the anti-cancer efficacy.In conclusion, the improved pharmacokinetic properties and anti-cancer activity of CUR could be achieved by preparing CUR-and PP85-loaded mesoporous silica nanoparticles.Incorporation of PP85, a surfactant that has P-gp inhibitory effect, into SMB7 together with CUR potentiated the anti-cancer effect of CUR in B16F10 melanoma-bearing mice by increasing the release and the intratumor concentration of CUR.