Simulation of adsorption and release of doxepin onto ZIF-8 including in vitro cellular toxicity and viability
Simulation of adsorption and release of doxepin onto ZIF-8 including in vitro cellular toxicity and viability
复制标题
模拟多塞平在 ZIF-8 上的吸附和释放，包括体外细胞毒性和活力
DOI：
10.1016/j.molliq.2021.115557
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发表时间：
2021-02-06
影响因子：
6
通讯作者：
Mahdavi, Behnam
中科院分区：
文献类型：
--
作者：
Dou, Xiaoliang;Keywanlu, Maryam;Mahdavi, Behnam
盐酸多塞平是一种抗抑郁药物，通常用于治疗轻到中度的抑郁症。然而，这种药物的口服生物利用度很差，可以进入血液的药物百分比很弱，而且变化很大。本研究旨在研究用于多塞平传递的ZIF-8纳米粒，并使用模拟材料工作室中的Gibbs系综蒙特卡罗方法评估这种药物在ZIF-8框架内的吸收和释放。这项研究还采用了一个模型来显示表面吸附剂(ZIF-8S)的性能。ZIF-8纳米骨架具有许多优点，如易于通过毛细血管，使药物释放到体循环，并防止高血浆浓度。此外，关于MOF的结构灵活性，该研究使用模拟分子动力学检查了药物分子的扩散。合适的负载量为8.6%，7.353×10~(-6)cm~(-2)/S多塞平分子从ZIF-8孔中缓慢扩散，证实该材料可作为多塞平的有效载体。此外，还使用了固定ZIF-8S模型，通过保持空腔的开口固定，从而获得了较高的负荷量12%。此外，由于乙醇已经作为一种合适的溶剂应用于许多生物体系中，因此在吸附的过程中，扩散过程也在这种溶剂中重复。因此，锌离子等吸附中心的存在可能会促进骨架与大分子的相互作用，从而提供理想的负载量和扩散量。此外，在乙醇存在下，ZIF-8分子筛表面能以较小的能量获得更大的吸附，这是由于溶剂分子的较大吸附所致。最后，为了确定制备的纳米颗粒在体外的细胞毒性和活性，用PC3人前列腺癌细胞处理它们，并通过四甲基偶氮唑盐比色法监测平均生长曲线。这项研究证实，与未处理的细胞相比，MTT信号减弱，因此ZIF-8可以降低所处理的癌细胞的代谢活性。这项研究表明，这种纳米材料可以作为多塞平的载体。(C)2021年爱思唯尔B.V.保留所有权利。
Doxepin hydrochloride is an antidepressant drug commonly used to treat mild to moderate depression. However, this drug has poor oral bioavailability, with the percentage of drug that can enter the bloodstream being weak and variable. The present study seeks to investigate the ZIF-8 nanoparticles for doxepin delivery and to assess this drug uptake and release in ZIF-8 frameworks using the Gibbs-ensemble Monte Carlo method in the Simulated Materials Studio. This study also adopted a model for showing surface adsorbent (ZIF-8S) capabilities. ZIF-8 nano-frameworks have many advantages such as easy flowing through capillaries leading to a satisfactory drug release into the systemic circulation and preventing high plasma concentration. Additionally, the study examined the diffusion of drug molecules using the simulated molecular dynamics with regard to the structural flexibility of the MOF. Proper loading of 8.6% and slow diffusion of 7.353 x 10(-6) cm(2)/s doxepin molecules from ZIF-8 pores confirmed that this material could be recommended as an effective carrier for doxepin. Furthermore, the fixed ZIF-8S model is also used by keeping the opening of cavities fixed, thereby attaining a higher loading amount 12%. Moreover, since ethanol has been applied as a suitable solvent in many biological systems, of adsorption, diffusion processes are also repeated in this solvent. Thus, presence of such adsorption sites as zinc ions may facilitate the interaction of the framework with large molecules to provide desirable loading and diffusion amounts. Furthermore, more adsorption can be reached with less energy at the surface of the ZIF-8 in the presence of ethanol, which is due to the greater adsorption of solvent molecules. Finally, to ascertain the in vitro cellular toxicity and viability of the prepared nanoparticles, they are treated with PC3 human prostate cancer cells and the average growth curves are monitored via MTT assay. This study confirmed a decrease in the MTT signal compared to the untreated cells, so ZIF-8 can reduce the metabolic activity of the performed cancer cells. This study shows that this nanomaterial can be achieved as a vehicle for delivery of doxepin. (C) 2021 Elsevier B.V. All rights reserved.