Multiphysics modeling and experiments on ultrasound-triggered drug delivery from silk fibroin hydrogel for Wilms tumor

• Published in: International journal of pharmaceutics 2022-06, Vol.621, p.121787-121787, Article 121787
• Main Authors: Gharehnazifam, Ziba, Dolatabadi, Roshanak, Baniassadi, Majid, Shahsavari, Hamid, Kajbafzadeh, Abdol-Mohammad, Abrinia, Karen, Gharehnazifam, Kimia, Baghani, Mostafa
• Format: Article
• Language: English
• Subjects: Hydrogel swelling; Multiphysics; Silk fibroin hydrogel; Stimulated drug delivery; Transient acoustics; Ultrasound
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.121787

[Display omitted] •The drug release rate can be enhanced up to 10 times through ultrasound stimulation over a non-stimulated release.•The drug release rate increases with ultrasound power and induction time until their peak, but decreases then.•Increasing exposure time can reach the peak release rates with lower power values.•The maximum cell death rate of Wilms tumor is at an ultrasound power of 1 W for 20 s.•Multiphysics simulation is a helpful tool for future potential predictions. In this study, silk fibroin hydrogel is employed as a carrier for vincristine and ultrasound as a method to accelerate the drug release. The Acoustic, deformation, swelling, and diffusion fields are coupled in a multi-physics model to optimize the drug delivery. A transient acoustic structure model and a chemically controlled mechanism are implemented, while a coupled model of deformation and diffusion takes the impact of mechanical forces into account. An evaluation of the model is made through experiments. To monitor the drug release rate over 40 days following injection of silk hydrogel syringes containing vincristine, they were triggered by ultrasound in some selected time intervals. Drug release rates were determined using different power intensities and induction times. Computed simulation results and laboratory experiments revealed that ultrasound could cause a significant improvement in drug release rate, with an increase of up to 10 times over a release without ultrasound stimulation. By increasing the ultrasound power and induction time up to their peak value, the drug release rate rises and drops then. Predictions of the drug release rate by the model were in good agreement with those observed in experiments. This makes the model a valuable tool for potential predictions. Results showed that the ultrasound triggers the increased cell death rates, but the Wilms tumor cells were resistant to higher concentrations of released drugs.