Fabrication of PCL-PEG-PCL nanocarrier for Co-loading of Docetaxel/Quercetin and assessment of its effect on growth inhibition of human liver cancer (Hep-G۲) cell line

Nanoscale co-delivery systems are advanced examples of combination therapies that can provide better therapeutic performance. Here, we tried to improve the solubility, bioavailability, synergistic, and potentiation properties of docetaxel (DTX) using co-loading of DTX and quercetin (Qu) into PCL-PEG-PCL-based nanocarrier. To this end, PCL-PEG-PCL copolymer synthesized, then, DTX and DTX/Qu loaded into this nanocarrier, separately, by the nanoprecipitation-modified method. Physicochemical and biological properties of nanocarriers were assessed on human liver cancer (Hep-G۲) and normal fibroblast cell lines, then, results were compared with free-DTX, free-Qu, and free-DTX/Qu groups. Based on the results, particles morphologically possessed a quasi-spherical shape with an average size of less than ۲۰۰nm. Moreover, DTX/Qu-coloaded nanocarrier was led to further inhibition of Hep-G۲ cells and lower inhibition of FNF cell viability, in a lower concentration (IC۵۰: ۲۹.۳۵ µg/ml) than DTX-loaded nanocarrier (IC۵۰: ۳۶.۷۳ µg/ml), free-DTX (IC۵۰: ۴۹.۸۱ µg/ml), and free-DTX/Qu (IC۵۰: ۳۷.۱۶ µg/ml). It could be due to the mixing of Qu and DTX that leads to an increase in the potentiation of DTX. The results also showed the release mechanism of Qu and DTX can be respectively diffusion (Fickian model) and a combination of dissolution and copolymer degradation (non-Fickian model). This was led to the higher inhibition of Hep-G۲ at lower concentration of drug and higher antioxidant activity of DTX/Qu-co-loaded nanocarrier than other groups, at lower inhibition of FNF cell growth. Accordingly, the synthesized nanocarriers showed a more impact on the inhibition of cancer cells compared to normal cells, due to the synergistic effect and the created potentiation.

Keywords:

Co-delivery System , Copolymer , Docetaxel , Potentiation Effect , Quercetin , Synergistic effect