Preparation and in vitro evaluation of an ultrasound-triggered drug delivery system: 10-hydroxycamptothecin loaded PLA microbubbles |
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Authors: | Hou Zhenqing Li Le Zhan Chuanming Zhu Peijuan Chang Di Jiang Qiwei Ye Shefang Yang Xiangrui Li Yang Xie Liya Zhang Qiqing |
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Institution: | a Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, PR China b Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192, PR China c First Hospital Affiliated to Xiamen University, Xiamen 361003, PR China |
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Abstract: | 10-Hydroxycamptothecin (HCPT) loaded PLA microbubbles, used as an ultrasound-triggered drug delivery system, were fabricated by a double emulsion-solvent evaporation method. The obtained microbubbles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and confocal laser scanning microscope (CLSM). In addition, the effect of diagnostic ultrasound exposure on BEL-7402 cells combined with HCPT-loaded PLA microbubbles was evaluated using cytotoxicity assay, CLSM and flow cytometry (FCM). It was found that the HCPT-loaded PLA microbubbles showed smooth surface and spherical shape, and the drug was amorphously dispersed within the shell and the drug loading content reached up to 1.69%. Nearly 20% of HCPT was released upon exposure to diagnostic ultrasound at frequency of 3.5 MHz for 10 min. Moreover, HCPT fluorescence in the cells treated only with the HCPT-loaded PLA microbubbles was discernible, but less intense, while those treated with the microbubbles in conjunction with ultrasound exposure was evident and intense, indicating an increased cellular uptake of HCPT by ultrasound exposure. Cytotoxicity test on BEL-7402 cells indicated that the HCPT-loaded PLA microbubbles combined with ultrasound exposure were more cytotoxic than the microbubbles alone. The results suggest that the combination of drug loaded PLA microbubbles and diagnostic ultrasound exposure exhibit an effective intracellular drug uptake by tumor cells, indicating their great potential for antitumor therapy. |
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Keywords: | Ultrasound contrast agent PLA 10-Hydroxycamptothecin Drug delivery system Ultrasound exposure |
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