Paclitaxel Nanoparticles Fabricated Through Supercritical Co2 Fluid Dynamic Solvent Method Demonstrate High Bioavailability

Abstract

In this study, Paclitaxel (PTX), a tricyclic diterpenoid lipophilic drug with high anti-cancer activity, was encapsulated within PEG-PCL by the Supercritical CO2 Fluid Dynamic Solvent Method (SCDSM) in comparison with the Solvent Evaporation Method (SEM). The nanoparticles produced by SCDSM had a size of 299.1 nm and a zeta potential of -9.52 mV respectively. A regular and spherical-shaped distribution of nanoparticles was identified through transmission electron microscope (TEM), and the success of entrapment was confirmed by in vivo distribution and kinetics experiments. The encapsulation efficiency of PTX was approximately 94.53%, and the loading efficiency was 31.49%. PTXNPS showed a distinct and smooth spherical shape via TEM. The in vitro release kinetics study indicated that PTXNPS was able to slow down the release rate of PTX in vitro. Pharmacokinetic analysis in rats demonstrated that the PTXNPS nanoparticles presented a larger AUC0-t and AUC0-∞, a longer Tmax, MRT, and a higher level of Cmax compared to free PTX. The nanoparticles effectively enhanced the distribution of the drug in the liver and spleen. This study provides a novel approach and method for the green, environmentally friendly, and efficient production of lipophilic drugs in nanoparticles, having strong commercialization and market promotion as well as application value.

Keywords: paclitaxel, nanoparticles, Supercritical CO2 Fluid Dynamic Solvent Method, PEG-PCL, Bioavailability