Construction of Curcumin and Paclitaxel Co-Loaded Lipid Nano Platform and Evaluation of Its Anti-Hepatoma Activity in vitro and Pharmacokinetics in vivo

PURPOSE: The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1–80:1 (w/w) designated “CU-PTX-LNP” and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method. METHODS: The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice. RESULTS: CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1–80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC(50) value of PTX of CU-PTX-LNP (by 5.47–332.7 times in HepG2 and 4.29–143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT((0-t);) CU: 4.31-fold, PTX: 4.61-fold) and half-life (t(1/2z;) CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs. CONCLUSION: The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations.