Controlled synergistic delivery of paclitaxel and heat from poly(β-amino ester)/iron oxide-based hydrogel nanocomposites

Poly(β-amino ester) (PBAE) biodegradable hydrogels were investigated for potential combined chemotherapeutic and heat delivery in the synergistic treatment of cancer. Hyperthermia, the heating of cancerous tissue from 41 to 45 °C, increases the efficacy of conventional cancer therapies such as irradiation and chemotherapy. The hydrogel nanocomposites in this work provide a drug delivery vehicle (via the biodegradable PBAE polymer network) and the ability to be heated remotely upon exposure to an alternating magnetic field (via iron oxide nanoparticles incorporated into the hydrogel matrix). PBAE macromers composed of poly(ethylene glycol) (N = 400) diacrylate (PEG400DA) or diethylene glycol diacrylate (DEGDA) with isobutylamine (IBA) were synthesized. Hydrogel nanocomposites were fabricated via free-radical polymerization to form a bulk hydrogel matrix entrapping both iron oxide nanoparticles and paclitaxel. The 2EG-IBA hydrogel exhibited complete degradation after approximately 7 weeks whereas the 9EG-IBA hydrogel degraded completely in 11 h. The hydrogels heated upon exposure to an alternating magnetic field throughout the degradation process. Additionally, the cytotoxicity of the degradation products was evaluated. Paclitaxel release was controlled via bulk degradation of the hydrogels. The tailorability of these nanocomposites makes them solid candidates for the synergistic treatment of cancer.