Bitargeted microemulsions based on coix seed ingredients for enhanced hepatic tumor delivery and synergistic therapy
Bitargeted microemulsions based on coix seed ingredients for enhanced hepatic tumor delivery and synergistic therapy
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基于薏苡仁成分的双靶向微乳剂用于增强肝肿瘤递送和协同治疗
DOI：
10.1016/j.ijpharm.2016.03.001
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发表时间：
2016-04-30
影响因子：
5.8
通讯作者：
Chen, Yan
中科院分区：
文献类型：
--
作者：
Qu, Ding;Sun, Wenjie;Chen, Yan
以薏苡仁油和薏苡仁多糖（CP）为抗癌成分，辅以功能性辅料，通过CP介导的被动肿瘤靶向性增强和半乳糖硬脂酸酯（肿瘤靶向配体）的修饰，制备了一种肝肿瘤双靶向微乳给药系统。在理化特性研究中，半乳糖硬脂酸酯修饰的薏苡仁多组分微乳（含30% CP（w%））（Gal-C-ME）具有良好限定的球形形状，具有小尺寸（47.63 +/-1.41nm）、窄的多分散指数（PDI，0.101 +/-0.002）和接近中性的表面电荷（-4.37 +/-1.76mV）。Gal-C-MEs对HepG 2细胞的半数抑制浓度（IC 50）为70.2mg/mL，比薏苡仁多组分微乳（C-MEs）降低了1.8倍。HepG 2细胞内化的异硫氰酸荧光素（FITC）-Gal-C-MEs（FITC-Gal-C-MEs）的荧光强度是FITC-C-MEs（FITC-C-MEs）的1.8倍，但当CP的重量比降低到10%时，后者的细胞摄取减少了1.6倍。在细胞凋亡研究中，C-ME（含有30%CP）与Gal-CME没有显示出显著差异，但相对于含有10%CP和20%CP的C-ME分别显示出3.3倍和1.5倍的增加。在体内肿瘤靶向研究中，Cy 5-Gal-C-MEs（Cy 5-Gal-C-MEs）在所有测试组中显示出最强的肿瘤组织蓄积和保留能力，其显著地分布在肿瘤部位，并且甚至在给药后48 h仍然存在。最重要的是，Gal-C-MEs与含有不同含量CP的C-MEs相比，具有更强的抑制肿瘤生长、延长生存时间和更有效的诱导肿瘤细胞凋亡的作用，进一步证实了一定量的CP和肿瘤靶向配体对有效的抗癌功效具有重要意义。上述结果表明，Gal-C-ME作为一种高效、安全的抗癌药物递送系统，具有增强肝癌递送的潜力。(C)2016爱思唯尔B. V.保留所有权利。
A hepatic tumor bitargeted microemulsions drug delivery system using coix seed oil and coix seed polysaccharide (CP) acting as anticancer components, as well as functional excipients, was developed for enhanced tumor-specific accumulation by CP-mediated enhancement on passive tumor targeting and modification of galactose stearate (tumor-targeted ligand). In the physicochemical characteristics studies, galactose stearate-modified coix seed multicomponent microemulsions containing 30% CP (w%) (Gal-C-MEs) had a well-defined spherical shape with a small size (47.63 +/- 1.41 nm), a narrow polydispersity index (PDI, 0.101 +/- 0.002), and a nearly neutral surface charge (-4.37 +/- 1.76 mV). The half-maximal inhibitory concentration (IC50) of Gal-C-MEs against HepG2 cells was 70.2 mg/mL, which decreased by 1.8-fold in comparison with that of coix seed multicomponent microemulsions (C-MEs). The fluorescence intensity of fluorescein isothiocyanate (FITC)-loaded Gal-C-MEs (FITC-Gal-C-MEs) internalized by HepG2 cells was 1.8-fold higher than that of FITC-loaded C-MEs (FIT C-C-MEs), but the cellular uptake of the latter became reduce by 1.6-fold when the weight ratio of CP decreased up to 10%. In the cell apoptosis studies, C-MEs (containing 30% CP) did not show a significant difference with Gal-CMEs, but exhibited 3.3-fold and 1.5-fold increase relative to C-MEs containing 10% CP and 20% CP, respectively. In the in vivo tumor targeting studies, Cy5-loaded Gal-C-MEs (Cy5-Gal-C-MEs), notably distributed in the tumor sites and still found even at 48 h post-administration, displayed the strongest capability of tumor tissue accumulation and retention among all the test groups. Most importantly, Gal-C-MEs had stronger inhibition of tumor growth, prolonged survival time and more effectively tumor cell apoptosis induction in comparison with C-MEs containing different amounts of CP, which further confirmed that a certain amount of CP and tumor-targeted ligand were of great importance to potent anticancer efficacy. The aforementioned results suggested that Gal-C-MEs presented promising potential as a highly effective and safe anticancer drug delivery system for enhanced liver cancer delivery. (C) 2016 Elsevier B.V. All rights reserved.