Ratio Design of Docetaxel/Quercetin Co-Loading-to-Nanocarrier: Synthesis of PCL–PEG–PCL Copolymer, Study of Drug Release Kinetic and Growth Inhibition of Human Breast Cancer (MCF-7) Cell Line

The present study aimed to design PCL–PEG–PCL copolymer as novel nanocarrier for co-loading of docetaxel (DTX) and quercetin (Qu) drugs and decrease side effects of the drug. To this end, tri-block-copolymer of PCL–PEG–PCL synthesized and DTX and Qu co-encapsulated into the mentioned nanocarrier with mass ratios of 0/0/20 (P0), 2/0/18 (P1), 4/0/16 (P2), 2/2/16 (P3), 4/4/12 (P4), respectively, by modified nano-precipitation method. Physicochemical and biological properties of nanocarriers were assessed. The results showed the mass ratio of 25% (w/w) has provided higher encapsulation efficiency (EE%) in nanocarrier (P2 and P3), so that EE% for DTX in P2 and P3 was 85.4%, 80%, respectively, as well as, for Qu in P3 was obtained 88%. Morphological results showed quasi-spherical shaped micelle along with mean diameters of 123 and 162 nm, for P2 and P3 nanocarriers, respectively. Based on the results, although the release behavior of drugs at pHs 7.2 and 5.5 was similar, and results were well fitted with the Higuchi model. However, there were 5.7 and 7.32% decrease in DTX release from P3 compared to P2, respectively at pHs 7.4 and 5.5, that related to pH-sensitive of nanocarrier, drugs co-loading, and their interactions into copolymer-matrix. Biologically, 50 µg/mL concentration of drug-coloaded nanocarriers was selected as optimum concentration for growth inhibition of more than 60% of cancerous cells, during 72 h. This study can indicate new insights into the design of drug-co-loaded nanocarriers and improve the synergistic and potentiation effect of drugs on the inhibition of cancer cells.