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Lipid-dendrimer nanohybrid system or dendrosomes: evidences of enhanced encapsulation, solubilization, cellular uptake and cytotoxicity of bortezomib
Applied Nanoscience ( IF 3.869 ) Pub Date : 2020-07-24 , DOI: 10.1007/s13204-020-01515-7
Vinay Kumar , Iliyas Khan , Umesh Gupta

Dendrimers are proven solubilizers of hydrophobic as well as hydrophilic drugs in its internal architecture. However, the toxicity of cationic dendrimers restricts its future possibilities as successful formulation. Hybrid systems such as lipid-dendrimer have shown great potential as drug delivery system due to their multifunctional adjustability, and biocompatibility. In the present study, liposomal dendrimer based nano-hybrid (called dendrosomes) of BTZ (bortezomib) were prepared and characterized through time-dependent transmission electron microscope (TEM) as well as photon correlation spectroscopy. Two types of prepared dendrosomes (DS1 and DS2) exhibited size of 145 ± 2.69 and 147 ± 3.26 nm, respectively. The overall hemolytic toxicity of the developed DS1 and DS2 dendrosomes was 4.96 ± 0.45 and 3.19 ± 0.32% (p < 0.005) respectively, which was lower than the dendrimeric formulation of BTZ encapsulated dendrimer (PD) at 50 ppm. Developed dendrosomes showed about 66.65 ± 1.5, and 69.03 ± 1.7% release of BTZ at pH 5.4 (72 h) from DS1 and DS2, respectively. Faster release of BTZ in case of acidic pH was in favour of the anti-tumor effectivity. The IC50 (minimum inhibitory concentration) values (216.9 ± 12.35 and 299.6 ± 21.61 nM) of DS1 and DS2, respectively against A549 cells were significantly lower in comparison to BTZ alone (p < 0.0001). BTZ loaded dendrosomes (DS1) exhibited higher cellular uptake in A549 cells, as evidenced by FITC (fluorescein isothiocyanate) tagged DS1 and DS2 cell uptake images. Overall, BTZ was attempted to be delivered through developed dendrosomes and evaluated. The effectiveness of BTZ was significantly improved against A549 cells compared to other nanoformulations.



中文翻译:

脂质-树状聚合物纳米杂化系统或树状体:硼替佐米的包封,增溶,细胞摄取和细胞毒性增强的证据

树状聚合物在其内部结构中被证明是疏水性和亲水性药物的增溶剂。但是,阳离子树状聚合物的毒性限制了其作为成功制剂的未来可能性。诸如脂质树状大分子的杂合系统由于其多功能的可调节性和生物相容性,已显示出作为药物递送系统的巨大潜力。在本研究中,制备了基于脂质体树状聚合物的BTZ(硼替佐米)纳米杂化物(称为树状体),并通过时变透射电子显微镜(TEM)以及光子相关光谱进行了表征。两种制备的树突体(DS1和DS2)的大小分别为145±2.69和147±3.26 nm。发达的DS1和DS2树突体的整体溶血毒性为4.96±0.45和3.19±0.32%(p 分别小于<0.005),低于50 ppm的BTZ包封的树枝状聚合物(PD)的树枝状配方。发达的树突体在pH 5.4(72 h)下分别从DS1和DS2释放出约66.65±1.5和69.03±1.7%的BTZ释放。在酸性pH条件下,BTZ的更快释放有利于抗肿瘤作用。与单独的BTZ相比,DS1和DS2分别针对A549细胞的IC 50(最低抑制浓度)值(216.9±12.35和299.6±21.61 nM)显着降低(p <0.0001)。载有BTZ的树状体(DS1)在A549细胞中表现出更高的细胞摄取,如FITC(异硫氰酸荧光素)标记的DS1和DS2细胞摄取图像所证明的。总体而言,尝试通过发达的树突小球递送BTZ并进行评估。与其他纳米制剂相比,BTZ对抗A549细胞的有效性显着提高。

更新日期:2020-07-24
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