Lipid nanoparticles loaded with 10-hydroxycamptothecin–phospholipid complex developed for the treatment of hepatoma in clinical application

Abstract

For the purpose of clinical intravenous injection of 10-hydroxycamptothecin, a novel formulation of lipid nanoparticles loaded with 10-hydroxycamptothecin–phospholipid complex (HCPT–PC–LNs) was prepared by solvent evaporation and high-pressure homogenization methods. Spherical particles with a mean particle size of 200 nm and high encapsulation efficiency of 97.39 ± 0.91% could be achieved under optimal conditions. In vitro release profile showed that the release pattern of HCPT from nanoparticles was retarded with neglectable initial burst release and well-fitted to Ritger-Peppas equation. In vivo distribution studies in mice showed that HCPT–PC–LNs were mainly localized in liver. Besides, in situ mouse hepatoma model was established and tumor uptake of HCPT–PC–LNs was much higher than that of free HCPT (more than 18-fold). It was found that HCPT–PC–LNs exhibited high growth inhibitory effect on human liver cancer cells by MTT assay. The cellular uptake of HCPT was 24.33 ± 1.30 × 10⁻⁷ μg/cell in HCPT–PC–LNs treated group at 12 h, which was almost 14-fold higher than that of free HCPT (1.72 ± 0.57 × 10⁻⁷ μg/cell). This study suggested that the HCPT–PC–LNs could be utilized as a novel formulation for liver tumors therapy, which might be applied in clinic in the near future.

Keywords::

• 10-Hydroxycamptothecin
• cellular uptake
• clinical application
• hepatoma uptake
• lipid nanoparticles
• phospholipid complex