Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound- triggered delivery of the hydrophobic drug, combretastatin A4
Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound- triggered delivery of the hydrophobic drug, combretastatin A4
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DOI：
10.1016/j.nano.2021.102401
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发表时间：
2021-07-22
影响因子：
5.4
通讯作者：
Coletta, P. Louise
中科院分区：
文献类型：
--
作者：
Charalambous, Antonia;Mico, Victoria;Coletta, P. Louise
药物的疏水性可能是其开发中的主要挑战，并阻止了高效抗癌剂的临床转化。我们使用了一种称为脂质-油-纳米液滴（LOND）的基于脂质的纳米乳剂，用于生物利用度差的考布他汀A4（CA 4）的包封和体内递送。在结肠直肠癌的异种移植模型中评估用CA 4 LOND的药物递送。LC-MS/MS分析显示，以比药物对照低四倍的药物剂量施用的CA 4 LOND在肿瘤内达到等同的CA 4浓度。然后，我们将CA 4 LOND连接到微泡（MB）上，并将该构建体靶向VEGFR 2。在CA 4 LONDs-MB处理的肿瘤中观察到肿瘤灌注的减少。与伊立替康联合治疗研究显示，与伊立替康单药治疗相比，肿瘤生长和灌注的降低幅度更大（P = 0.01）。这项研究表明，LOND，无论是单独的或连接到靶向MB，有可能显着提高肿瘤特异性疏水性药物输送。(C)2021年，任作家。爱思唯尔公司出版
The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer. LC-MS/MS analysis revealed that CA4 LONDs, administered at a drug dose four times lower than drug control, achieved equivalent concentrations of CA4 intratumorally. We then attached CA4 LONDs to microbubbles (MBs) and targeted this construct to VEGFR2. A reduction in tumor perfusion was observed in CA4 LONDs-MBs treated tumors. A combination study with irinotecan demonstrated a greater reduction in tumor growth and perfusion (P = 0.01) compared to irinotecan alone. This study suggests that LONDs, either alone or attached to targeted MBs, have the potential to significantly enhance tumor-specific hydrophobic drug delivery. (C) 2021 The Authors. Published by Elsevier Inc.