Active Scaffolds for On-demand Drugs and Cell Delivery #4

We suggested that the deformation of the gel under the influence of a magnetic field, water convection and related forces could accelerate the process of drug emission from ferrogel capsules or cells attached to the pore surfaces of macroporous ferrogel. To test this hypothesis, we selected mitoxantrone (Mr 444 444) as a drug sample. Ferrogels, each containing 300 mg of mitoxantrone, were placed in a sodium phosphate buffer (PBS). Every 30 minutes, one group of ferrogels was subjected to 120 cycles of appearance/disappearance of the magnetic field for 2 minutes by manual placement and removal of a permanent magnet to the gels, while other gels were not affected by the magnetic field.




The successive deformation and return to the initial state contributed to the accelerated release of mitoxantrone from the gel. The total amount of the isolated drug was ~7 times more than that of the gel without exposure to a magnetic field for 3 hours (Fig. 3A). These experiments were also conducted with plasmids (Mr~106) condensed with polyethylenimine (PEI, Mr~22,000) and chemokine SDF-1 (Mr 8,000) to establish whether such an approach could be used for a more extensive selection of potential drugs. Indeed, an increase in drug release was observed when exposed to a magnetic field relative to the gels from the control group (Fig. 3B and C).



Then we used macroscopic ferrogels to study regulated cell isolation in vitro (Fig. 4A). RGD on alginate in the gel allows cells to adhere to a porous surface, and the strength of adhesion increases in proportion to the amount of RGD. The initial level was the amount of 7.43 mmol RGD per gram of alginate. A ratio of 50% and 10% of the amount of RGD from the initial level was also chosen to study the role of the gel in adhesion. For this purpose, human dermal fibroblasts (1.5 x 106) were used, seeded on each of the gels. Then the gels were incubated for 4 hours at 37C for cell adhesion. After that, the gels were subjected to 120 cycles of switching on/off the magnetic field for ~ 2 minutes with a 2-hour interval. Cell isolation was evaluated as a function of time (Fig. 4B). The effect of the magnetic field led to a powerful release of cells, and the intensity of the release itself differed depending on the amount of RGD. After 6 hours (3 cycles of magnetic stimulation), about a third of the cells were isolated from the gel with an amount of RGD of the initial level, while already half of the cells were isolated in gels with an amount 50% less than the initial one. Gels with an amount of RGD of 10% of the original produced the release of more than 90% of cells after 4 hours (2 cycles of magnetic stimulation). This suggests that with a decrease in the amount of RGD, cell adhesion decreases and the number of cells ejected under the influence of a magnetic field increases. More than 95% of the cells were viable, they were placed in a Petri dish at 37C. Two days later, the cells continued to function normally (Fig. 4C).


After 1 hour after implantation, the gels were subjected to 120 cycles of switching on/off the external magnetic field by inserting and pulling a magnet over the gel near the mouse skin. escortannonce.net/escorts/geneve/
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