Silk Fibroin Hydrogel Reinforced With Magnetic Nanoparticles as an Intelligent Drug Delivery System for Sustained Drug Release.

Due to the well-known biocompatibility, tunable biodegradability, and mechanical properties, silk fibroin hydrogel is an exciting material for localized drug delivery systems to decrease the therapy cost, decrease the negative side effects, and increase the efficiency of chemotherapy. However, the lack of remote stimuli response and active drug release behavior has yet to be analyzed comparatively. In this study, we developed magnetic silk fibroin (SF) hydrogel samples through the facile blending method, loaded with doxorubicin hydrochloride (DOX) and incorporated with different concentrations of iron oxide nanoparticles (IONPs), to investigate the presumable ability of controlled and sustained drug release under the various external magnetic field (EMF). The morphology and rheological properties of SF hydrogel and magnetic SF hydrogel were compared through FESEM images and rheometer analysis. Here, we demonstrated that adding magnetic nanoparticles (MNPs) into SFH decreased the complex viscosity and provided a denser porosity with a bigger pore size matrix structure, which allowed the drug to be released faster in the absence of an EMF. Release kinetic studies show that magnetic SF hydrogel could achieve controlled release of DOX in the presence of an EMF. Furthermore, the drug release from magnetic SF hydrogel decreased in the presence of a static magnetic field (SMF) and an alternating magnetic field (AMF), and the release rate decreased even more with the higher MNPs concentration and magnetic field strength. Subsequently, Wilms' tumor and human fibroblast cells were cultured with almost the same concentration of DOX released in different periods, and cell viability was investigated using MTT assay. MTT results indicated that the Wilms' tumor cells were more resistant to DOX than the human fibroblasts, and the IC50 values were calculated at 1.82 ± 0.001 and 2.73 ± 0.004 (µg/ml) for human fibroblasts and Wilms' tumor cells, respectively. Wilms' tumor cells showed drug resistance in a higher DOX concentration, indicating the importance of controlled drug delivery. These findings suggest that the developed magnetic SFH loaded with DOX holds excellent potential for intelligent drug delivery systems with noninvasive injection and remotely controlled abilities.

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

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.

Computational analysis of vincristine loaded silk fibroin hydrogel for sustained drug delivery applications: Multiphysics modeling and experiments.

In this paper, silk fibroin hydrogel is used as a drug carrier for vincristine. To optimize drug delivery, a multi-physics model is proposed that couples the deformation and diffusion fields. We applied inverse analysis and general continuum mechanics to define material parameters and mechanical properties. To examine the mass transport and chemical behavior, an affinity-based diffusion and degradation of a drug-loaded polymer matrix is employed. Some experiments are carried out to examine the capability of the presented model. After preparing the vincristine loaded silk hydrogel syringes, they were injected into PBS and enzyme solutions to monitor the drug release rate for 40 days. Obtained results from the computational simulation and laboratory tests showed that the silk fibroin hydrogel was deswelled after about 40 days in enzyme solution. Degradation led to faster and higher doses of vincristine drug release in comparison to the case of PBS solution. Results revealed that more than 80% of the drug was released in the first 5 days in the enzyme solution, but in PBS solution only 10% of the drug was released during 40 days. The model predictions of deswelling behavior and drug release rate were in good agreement with those of experimental results. Therefore, it can be employed as a reliable tool for further predictions.