Folic Acid-Targeted Mixed Pluronic Micelles for Delivery of Triptolide

The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA-F-127/F-68-TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA-F-127/F-68-TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA-F-127/F-68-Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA-F-127/F-68-Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA-F-127/F-68-Nr, the fluorescence imaging system showed that FA-F127/F-68-Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA-F-127/F-68-TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA-F-127/F-68-TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA-F-127/F-68-TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA-F-127/F-68-TPL represents a promising antitumor drug delivery system.