Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model
Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model
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DOI：
10.1016/j.actbio.2015.03.014
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发表时间：
2015-06-01
影响因子：
9.7
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
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作者：
Abdalkader, Rodi;Kawakami, Shigeru;Hashida, Mitsuru
本研究研制了一种含有阿霉素和全氟丙烷气体（DLMB）的新型磷脂基微泡制剂。在全氟丙烷（PFP）气体存在下，通过磷脂分散体的机械搅拌制备了dlmb。选择阴离子磷脂二硬脂酰磷脂酰甘油（DSPG）通过静电相互作用将阿霉素加载到微泡中。测定了dlmb的粒径、zeta电位、回声性和稳定性。载药量>= 92%。在荷瘤小鼠中评估了dlmb作为一种治疗方式的潜力。PFP的气相色谱分析表明，当阿霉素在相当于DSPG的10-82%浓度下使用时，PFP的保留率显著提高。超声（US）照射联合dlmb增强了体外对B16BL6黑色素瘤小鼠细胞增殖的抑制作用。此外，体内dlmb联合（US）照射可显著抑制小鼠B16BL6黑色素瘤的生长。此外，超声成像显示肿瘤血管内dlmb的高对比度增强。这些结果表明，dlmb可以作为US触发的阿霉素载体以及肿瘤显像剂用于癌症治疗。(C) 2015材料学报Elsevier Ltd.出版。版权所有。
In this study, a novel phospholipid-based microbubble formulation containing doxorubicin and perfluoropropane gas (DLMB) was developed. The DLMBs were prepared by mechanical agitation of a phospholipid dispersion in the presence of perfluoropropane (PFP) gas. An anionic phospholipid, distearoyl phosphatidylglycerol (DSPG) was selected to load doxorubicin in the microbubbles by means of electrostatic interaction. The particle size, zeta potential, echogenicity and stability of the DLMBs were measured. Drug loading was >= 92%. The potential of the DLMBs for use as a theranostic modality was evaluated in tumor bearing mice. Gas chromatography analysis of PFP showed significant enhancement of PFP retention when doxorubicin was used at concentrations of 10-82% equivalent to DSPG. The inhibitory effects on the proliferation of B16BL6 melanoma murine cells in vitro were enhanced using a combination of ultrasound (US) irradiation and DLMBs. Moreover, in vivo DLMBs in combination with (US) irradiation significantly inhibited the growth of B16BL6 melanoma tumor in mice. Additionally, US echo imaging showed high contrast enhancement of the DLMBs in the tumor vasculature. These results suggest that DLMBs could serve as US triggered carriers of doxorubicin as well as tumor imaging agents in cancer therapy. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.