Synthesis of Functionalized Polycaprolactones for Drug Delivery Applications

Polycaprolactones (PCLs) have been used in various applications due to their biodegradability, biocompatibility, and favorable mechanical properties. The ability to attach multiple functionalities in the PCL backbone can provide many possibilities to tune the polymer’s physicochemical properties. Among the applications, extensive efforts have been dedicated to developing PCLs as carriers of bioactive compounds; however, some limitations still encountered are low payload, instability, and uncontrolled release of the cargo. In this work, micellar drug delivery systems obtained from the self-assembly of amphiphilic block copolymers comprising of benzyloxy- and oligo(ethylene glycol)-substituted PCLs were designed to load the doxorubicin anticancer drug and a quercetin cardioprotective polyphenol. The co-loading approach provided a way to enhance the loading capacity of the micelle for both cargoes. The utilization of various lengths of oligo(ethylene glycol) side-chains permitted tuning of the polymer’s thermoresponsive behavior to modulate the release of the cargo. These micelles exhibited a low critical micelle concentration, which is necessary for tolerating severe dilutions. Many copolymers have been explored for drug delivery; however, amphiphilic homopolymers can also be an alternative due to their more straightforward synthesis. Most reported amphiphilic homopolymers have a nonbiodegradable backbone, exhibits pH-dependent assembly, and are charged. Herein, non-ionic amphiphilic PCL homopolymers readily self-assembled to form micelles. The potential of using these micelles as drug carriers were explored by loading a eugenol anti-inflammatory molecule.