Subcutaneous mesoporous silica formulation modulates systemic and tumor-associated paclitaxel exposure in a B16F10...

Paclitaxel, a widely used chemotherapeutic agent for solid tumors, is primarily administered by intravenous infusion. Although subcutaneous administration has been investigated as a patient-centered alternative, developing subcutaneous paclitaxel formulations remains challenging. In this study, a mesoporous silica nanoparticle-based formulation (PCT112) containing paclitaxel, curcumin, and D-α-tocopheryl polyethylene glycol succinate was developed to modulate systemic and tumor-associated drug exposure after subcutaneous administration. PCT112 showed high encapsulation efficiencies for paclitaxel and curcumin and enabled amorphous drug incorporation within the silica matrix, resulting in sustained release and an increased paclitaxel solubility. In B16F10 melanoma cells, PCT112 showed time-dependent cytotoxicity, increased spheroid uptake, a delayed increase in apoptosis, and more pronounced microtubule disruption than free paclitaxel. In 3-dimensional multicellular tumor spheroids, higher Uptake Index values were associated with greater inhibition of spheroid growth. In B16F10 tumor-bearing mice, repeated subcutaneous administration of PCT112 produced dose-dependent tumor growth suppression and prolonged survival. Pharmacokinetic analysis showed delayed absorption and extended systemic exposure, whereas biodistribution analysis revealed dose-dependent increases in tumor-associated paclitaxel concentrations, which remained detectable over the observation period. Compared with intravenous Abraxane, longitudinal tumor-growth trajectories differed over time, while no statistically significant difference was observed at the final treatment day. Body-weight trajectories differed between the two groups. Collectively, these findings suggest that mesoporous silica-mediated subcutaneous delivery may support a lower-peak, prolonged exposure profile while increasing tumor-associated drug exposure, warranting further preclinical investigation for hydrophobic anticancer agents such as paclitaxel.