Preparation And In Vitro And In Vivo Ultrasound Imaging Of Poly (Lactic Acid) Nanobubbles As Contrast Agent

Objective: Ultrasound contrast agents commonly used in the market are micron-sized and cannot penetrate the blood vessel wall,so blood pool imaging can only be performed,and tumor imaging cannot be performed.The nanobubbles involved in this study belong to the nano-level contrast agent,which can achieve tumor imaging,and has the advantages of good stability and modification.Methods: The polylactic acid of suitable molecular weight was synthesized by the ring-opening polymerization of lactide,and the characterization of nuclear magnetic,infrared and molecular weight were carried out.The polylactic acid of suitable molecular weight was selected as the carrier material,and the encapsulation of perfluorocarbon was prepared by emulsification-solvent evaporation method.The nanobubbles of perfluorocarbon were characterized by particle size,potential,morphology and other properties.The physical stability of the nanobubbles was investigated,the biocompatibility of the nanobubbles was preliminarily evaluated,and then the in vitro phase transition properties of the nanobubbles were studied.Finally,the subcutaneous properties of the animals were constructed.A tumor model was performed in vivo ultrasound enhanced imaging studies.Results: The characterization of nanobubbles proved that the average particle size of the prepared nanobubbles was 318.4±5.1 nm,and the PDI was 0.167±0.020,indicating that the nanobubble particle size was nanometer-scale and could be stably maintained at the nanometer level for a long time.The compatibility evaluation indicated that the nanobubbles were non-cytotoxic and did not cause hemolysis of the cells,which verified the safety of the nanobubbles.Ultrasound imaging and fracture experiments showed that the nanobubbles had good imaging results in vitro,and tumor-targeted release was possible in the later stage.Related research on drugs;through the study of in vitro phase transition behavior,the optimal development conditions for nanobubbles were 25°C~37°C,in vivo ultrasound imaging studies were performed by constructing nude mouse models of subcutaneous tumors in nude mice.The results show that the nanobubbles have a good tumor imaging effect.Conclusion: Experiments had shown that nanobubbles could be performed contrast-enhanced ultrasound imaging compared to micron-sized contrast agents.