Enhancement of Loading Efficiency by Coloading of Doxorubicin and Quercetin in Thermoresponsive Polymeric Micelles

Chemotherapy faces challenges, including poor aqueous solubility of the drugs, and cardiotoxicity. Micellar drug delivery systems (DDS) are used to encapsulate anticancer drugs for better therapeutic effects, however, with poor loading content. Herein, we synthesized a micellar DDS using gamma-benzyloxy substituted poly(epsilon-caprolactone) as the hydrophobic block and coloaded anticancer doxorubicin (Dox) and antioxidant quercetin (Que). gamma-Substituted oligo(ethylene) glycol (OEG) poly(epsilon-caprolactone)s were used as hydrophilic blocks to make the polymers thermoresponsive. Variation of the OEG chain allowed the tunability of the lower critical solution temperature. Moreover, drug loading and release were studied. Thermodynamic stability, size, and morphology were determined by fluorescence measurements, dynamic light scattering, and transmission electron microscopy. Combination loading demonstrated improved loading of Dox and Que. Biological studies were performed using HepG2 human liver cancer and H9c2 rat heart cells. The use of biodegradable, biocompatible, and thermoresponsive polymers along with the coloading approach is a good strategy in developing DDSs.