Preparation and in vitro evaluation of an ultrasound-triggered drug delivery system: 10-Hydroxycamptothecin loaded PLA microbubbles

• Published in: Ultrasonics Vol. 52; no. 7; pp. 836 - 841
• Main Authors: Hou, Zhenqing, Li, Le, Zhan, Chuanming, Zhu, Peijuan, Chang, Di, Jiang, Qiwei, Ye, Shefang, Yang, Xiangrui, Li, Yang, Xie, Liya, Zhang, Qiqing
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.09.2012; Elsevier
• Subjects: 10-Hydroxycamptothecin; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Biological and medical sciences; Calorimetry, Differential Scanning; Camptothecin - analogs & derivatives; Camptothecin - chemistry; Camptothecin - pharmacology; Cardiovascular system; Chromatography, High Pressure Liquid; Cytotoxicity Tests, Immunologic; Drug delivery system; Drug Delivery Systems; Flow Cytometry; In Vitro Techniques; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Microbubbles; Microscopy, Confocal; Microscopy, Electron; Miscellaneous. Technology; PLA; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Technology. Biomaterials. Equipments. Material. Instrumentation; Transducers; Ultrasonic investigative techniques; Ultrasonics; Ultrasound contrast agent; Ultrasound exposure; X-Ray Diffraction; Ultrasound contrast agent; 10-Hydroxycamptothecin; Ultrasound exposure; PLA; Drug delivery system; Therapy; Spherical shape; Fluorescence; Cytotoxicity; Bubble; Shell; Scanning microscope; Emulsion; Acoustic image; Contrast media; Human; Scanning electron microscopy; Drug combination; Drug dispensation; X ray diffraction; Laser microscope; Transmission electron microscopy; Calorimetry; Medical imagery; Intracellular
• ISSN: 0041-624X; 1874-9968
• DOI: 10.1016/j.ultras.2011.10.009

► Lactone-formed 10-hydroxycamptothecin (HCPT) loaded PLA microbubbles were fabricated by a double emulsion–solvent evaporation method. ► The HCPT loaded PLA microbubbles had the typical characteristics of drug carrier, and possessed ultrasound-triggered drug release mechanism. ► The HCPT loaded PLA microbubbles combined with ultrasound exposure showed more cytotoxic than the microbubbles alone. ► The combination of drug loaded microbubbles and diagnostic ultrasound exposure exhibit an effective intracellular drug uptake by tumor cells, indicating their great potential for antitumor therapy. 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 3.5MHz for 10min. 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.