Lipid-polymer hybrid nanoparticles (LPNs) are promising drug delivery systems in various of disease treatment areas, particularly for cancer treatments. Here, a water-insoluble antitumor agent, hydroxycamptothecin (HCPT), was successfully incorporated into LPNs formed from polylactic-co-glycolic acid (PLGA), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) (DSPE-PEG2000), and lecithin, by a modified single emulsification-solvent evaporation method. Quality-by-design (QbD) strategy composed of Plackett-Burman and Box-Behnken designs were applied for optimizing HCPT-LPNs with desired properties. The optimized HCPT-loaded lipid-polymer hybrid nanoparticles (HCPT-LPNs) were on the nanoscale, with a final size of 220.9 nm, drug loading of 2.50%. HCPT-LPNs were highly stable in plasma and had pH- and drug loading-related sustained release characteristics. The in vitro cytotoxicity of HCPT-LPNs against MCF-7 and HepG2 cells showed that HCPT-LPNs had higher in vitro cytotoxicity than HCPT solution (HCPT-Sol) with reduced cell viability and IC50 values. In vivo pharmacokinetic assays demonstrated that the AUC of HCPT-LPNs was more than 3 times higher than that of HCPT-Sol after tail vein injection in SD rats. Tumor growth was significantly inhibited compared with HCPT-Sol after a single tail vein injection of HCPT-LPNs in murine LLC-GFP-luc lung cancer bearing mice at a dose of 6 mg/kg, without severe side effects. These results indicate that HCPT-LPNs are the promising drug delivery system for antitumor treatments.
Keywords: Antitumor effect; Hydroxycamptothecin; Lipid-polymer hybrid nanoparticles; Phamacokinetic; Quality-by-design.
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