Preparation of span-poly(ethylene glycol) ultrasound contrast agent microbubbles combined with folate-carbon nano tube-paclitaxel / 中国组织工程研究

ABSTRACT

BACKGROUND:As the sensitivity, clarity and accuracy of traditional ultrasound contrast agents are easy to be affected by objective factors, it is difficult to achieve diagnose and therapy simultaneously. Carbon nano tubes (CNTs) possess a specific reticular, hol ow and tubular structure and the potential to enhance the ultrasound imaging. The functional CNTs obtained through non-covalent adsorption, covalent bonding and internal embedding hold a good biocompatibility and high drug loading efficiency. So the drug loaded CNTs are added into the microbubble to synthesize a multi-functional ultrasound contrast agent. OBJECTIVE:To prepare the span-poly(ethylene glycol) (span-PEG) ultrasound contrast agent microbubble combined with folate-CNTs-paclitaxel (FA-CNTs-PTX) and to investigate its appearance, particle size as wel as loading efficiency of CNTs and PTX. METHODS:Firstly, the span-PEG microbubble was prepared using the acoustic cavitation method and its preparation process was optimized through the orthogonal experiment. Then the FA-CNTs-PTX compound was synthesized by the electrostatic self-assembly andπ-πadsorption principle. In the end, the span-PEG ultrasound contrast agent microbubble combined with FA-CNTs-PTX was obtained by loading the FA-CNTs-PTX into the span-PEG microbubble. The appearance of the composite microbubble were observed using scanning and transmission electron microscopes, the distribution and average particle size were detected by laser particle size analyzer, and the loading efficiency of CNTs and PTX was measured through ultraviolet spectroscopy. RESULTS AND CONCLUSION:The composite microbubble had a smooth surface and the average particle size was 442 nm. The loading efficiency of CNTs and PTX in the composite microbubble was 1.69%and 47.9%, respectively. To conclude, the FA-CNTs-PTX targeting drug delivery system is successful y loaded into the span-PEG microbubble. The composite microbubble is a hol ow sphere that has uniform nanoscaled particle size distributions, which is expected to become an ideal ultrasound contrast agent involved in angiography and targeting therapy.