Low-melting-point polymeric nanoshells for thermal-triggered drug release under hyperthermia condition

Abstract

Purpose: The aim of this paper was to synthesise core-shell nanostructures comprised of mesoporous silica core and a low melting-point polyethylene glycol (PEG) nanoshell with a sharp gel-liquid phase transition for rapid drug release at hyperthermia temperature range. Materials and methods: The phase transition behaviours of PEGs with molecular weights of 1000, 1500, and 2000 Da were analysed using differential scanning calorimetry (DSC) to determine the optimal formulation with phase transition in the hyperthermia range. The 'graft-to' method was employed to synthesise core-shell nanostructures using the selected PEG formulation. The drug loading and release behaviours of these nanocarriers were examined by ultra-violet visible spectroscopy (UV-Vis) using doxorubicin as a model drug. Magnetic resonance-guided focused ultrasound (MRgFUS) was also applied as a typical thermal modality to evaluate the rate of drug release from the core-shell nanostructures. Results: The PEG molecular weight of 1500 Da presented the optimal phase transition temperature for thermal-triggered release under hyperthermia conditions. Drug release measurements at different temperatures using UV-Vis methods showed a 20.2 ± 4.3% leakage in aqueous solution at 37 °C after 30 min, while this value was significantly increased to 68.2 ± 3.7% at 50 °C. A 45.5 ± 3.1% drug release was also obtained after sonication of the drug-loaded nanoparticles for 5 × 20 s using MRgFUS. Conclusion: Although the ratio of drug leakage at physiological temperatures was relatively high, the sharp transition temperature, high loading efficiency, and fast drug release at hyperthermia temperature range could make these core-shell nanoparticles prominent for enhancing the efficacy of various hyperthermia modalities in the treatment of cancer tumours.