A new PLA-Tween composited drug-carrying C60-Fe3O4 multifunctional ultrasound contrast agent based on three kinds of lesions

A PLA-Tween composited drug-carrying C60-Fe3O4 microbubble was designed and prepared. Using Fe3O4 as a targeting factor and C60 as a drug carrier, warfarin (WF), netimixin (NET) and doxorubicin (DOX) respectively were loaded on a C60-Fe3O4 complex through pi-pi conjugate effect, and C60-Fe3O4-WF, C60-Fe3O4-NET and C60-Fe3O4-DOX targeted drug-loading complexes were obtained. The three drug-loading complexes were respectively combined into PLA and Tween membrane material, PLA-Tween composited C60-Fe3O4-DOX microbubbles, PLA-Tween composited C60-Fe3O4-NET microbubbles and PLA-Tween composited C60-Fe3O4-WF microbubbles were obtained, respectively. The average particle size of PLA-Tween composited drug-carrying C60-Fe3O4 microbubbles was 446.4 nm, the microbubble size was uniform, and the Zeta potential was -40.5 mV which showed a good stability. The loading rates of DOX, NET and WF in PLA-Tween composited drug-carrying C60-Fe3O4 microbubbles were 5.58%, 8.15% and 3.37%, respectively. PLA-Tween composited C60-Fe3O4-DOX microbubbles could inhibit the breast cancer MDA-MB-231 cells and normal mouse fibroblast 3T3 cells, the inhibition rates were respectively 53.4% and 18.6%, which significantly reduced the toxicity of free DOX drug on the normal cells (62.2%). PLA-Tween composited C60-Fe3O4-NET microbubbles had a inhibitory effect on the growth of Staphylococcus aureus and Escherichia coli, and the inhibitory effect on Escherichia coli was better. PLA-Tween composited C60-Fe3O4-WF microbubbles could inhibit the formation of thrombus, and PT, TT and APTT were significantly prolonged. PLA-Tween composited C60-Fe3O4 microbubbles had a developing effect on the kidney, bladder and abdominal aorta of rabbit. Under the action of external magnetic field, the ultrasonic imaging effect of composite microbubbles was significantly enhanced.

Automated summary

A targeted drug-carrying microbubble system was designed and prepared, which showed promising drug-loading capabilities and stability for various drugs targeting different diseases.