A Quantitative Study of Thermal and Non-thermal Mechanisms in Ultrasound-Induced Nano-drug Delivery

Objective: The primary objective of this study was to quantify the contributions to drug release for thermal and non-thermal mechanisms in ultrasound-induced release from gold nanoparticles (GNPs) for the first time.Methods: We studied doxorubicin (DOX) and curcumin release from the surface of GNPs using two different meth-ods to induce drug release in an ex vivo tissue model: (i) localized tissue heating with a water bath and (ii) low-intensity pulsed ultrasound (LIPUS) exposure. Both methods have similar temperature profiles and can induce the release of both hydrophobic (curcumin) and hydrophilic (DOX) drugs from the surface of GNPs. Quantitative drug release in both cases was compared via fluorescence measurements.Discussion: The water bath heating method induced drug release using thermal effects only, whereas LIPUS expo-sure induced drug release used a combination of thermal and non-thermal mechanisms. It was found that there were increases of 70 +/- 16% (curcumin) and 127 +/- 20% (DOX) in drug release when LIPUS was used to induce drug release (both thermal and non-thermal mechanisms) as compared with the water bath (thermal mechanisms only) mediated release.Conclusion: We determined that non-thermal mechanisms account for 41 +/- 3% of curcumin release and 56 +/- 4% of DOX release. It was concluded that in our ex vivo tissue model, the non-thermal mechanisms play a significant role in LIPUS-induced drug release from GNP drug carriers and that the contributions of non-thermal mechanisms to drug release depend on the type of anticancer drug loaded on the GNP surface.