Jermy B Rabindran, Ravinayagam Vijaya, Almohazey D, Alamoudi W A, Dafalla H, Akhtar Sultan, Tanimu Gazali
Department of Nano-Medicine Research, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, 31441 Dammam, Saudi Arabia.
Deanship of Scientific Research & Department of Nano-Medicine Research, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, 31441 Dammam, Saudi Arabia.
Appl Clay Sci. 2022 Jan;216:106333. doi: 10.1016/j.clay.2021.106333. Epub 2021 Nov 9.
Dexamethasone (Dex) is used in drug regimen for treatment of Coronavirus disease (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fusion and entry into the cell occurs at pH 5.5. In our present study, we have identified a green, cheap clay based halloysite (Hal) nanoformulation with release capability of Dex at such interactive pH condition. 30%ZnFeO/Hal and 30%NiFeO/Hal were prepared by one-pot synthesis technique. Dex (5% wt/wt) was functionalized over both nanocomposites. Finally, polyethylene glycol (PEG) was coated over ZnFeO/Hal/Dex and NiFeO/Hal/Dex nanocomposite using lyophilization technique (0.08 μl/mg of nanocarrier). The release ability of Dex was studied under pulmonary infection and normal pH conditions (pH = 5.6 and 7.4). The characterization study using X-ray diffraction (XRD) and UV-visible diffuse reflectance (DRS) spectra confirmed the presence of spinel ferrites over Hal. Nitrogen adsorption isotherm showed the surface area of ZnFeO/Hal (75 m/g), pore volume (0.27 cm/g) with average pore size (14.5 nm). Scanning electron microscope/Energy dispersive spectroscopy (SEM-EDS) and Transmission electron microscopy analysis revealed a textural change in halloysite tubular type indicating drug adsorption and PEG adhesion. DRS spectra indicated an intergrowth of zinc ferrite nanoparticles on the halloysite nanotubes. Interestingly, ZnFeO/Hal/Dex/PEG exhibited a high Dex release ability (17.5%, 168 h) at pH = 5.6 relevant to SARS-CoV-2 fusion entry into the cell pH condition of 5.5. Comparatively, the nanocomposite showed a less Dex release (<5%) release for 168 h at neutral pH = 7.4. The drug release kinetics were studied and the obtained data were fitted for the release constant and release exponent, using the Korsmeyer-Peppas model. To test the compatibility of our nanocomposites, we performed the cell viability assay (MTT) using HEK293 cells. Our results showed that at 0.3 mg/ml, Dex-loaded nanocomposite had a statistically significant improvement in cell viability compared to Dex alone. These results suggest that our nanocomposite has prevented the toxic effect of Dex and has huge potential to act as pulmonary drug delivery system for targeted lung infection therapeutics.
地塞米松（Dex）用于治疗冠状病毒病（COVID - 19）的药物方案中。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在pH 5.5时融合并进入细胞。在我们目前的研究中，我们已经确定了一种绿色、廉价的基于粘土的埃洛石（Hal）纳米制剂，其在这种相互作用的pH条件下具有地塞米松释放能力。通过一锅合成技术制备了30%ZnFeO/Hal和30%NiFeO/Hal。将地塞米松（5%重量/重量）在两种纳米复合材料上进行功能化。最后，使用冻干技术（0.08 μl/mg纳米载体）在ZnFeO/Hal/Dex和NiFeO/Hal/Dex纳米复合材料上包覆聚乙二醇（PEG）。研究了地塞米松在肺部感染和正常pH条件（pH = 5.6和7.4）下的释放能力。使用X射线衍射（XRD）和紫外可见漫反射（DRS）光谱进行的表征研究证实了埃洛石上存在尖晶石铁氧体。氮气吸附等温线显示ZnFeO/Hal的表面积为75 m²/g，孔体积为0.27 cm³/g，平均孔径为14.5 nm。扫描电子显微镜/能量色散光谱（SEM-EDS）和透射电子显微镜分析揭示了埃洛石管状结构的纹理变化，表明药物吸附和PEG粘附。DRS光谱表明锌铁氧体纳米颗粒在埃洛石纳米管上共生。有趣的是，ZnFeO/Hal/Dex/PEG在与SARS-CoV-2融合进入细胞pH条件5.5相关的pH = 5.6时表现出高地塞米松释放能力（17.5%，168小时）。相比之下，该纳米复合材料在中性pH = 7.4时168小时内地塞米松释放较少（<5%）。研究了药物释放动力学，并使用Korsmeyer-Peppas模型将获得的数据拟合为释放常数和释放指数。为了测试我们纳米复合材料的兼容性，我们使用HEK293细胞进行了细胞活力测定（MTT）。我们的结果表明，在0.3 mg/ml时，与单独的地塞米松相比，负载地塞米松的纳米复合材料在细胞活力方面有统计学上的显著改善。这些结果表明，我们的纳米复合材料预防了地塞米松的毒性作用，并且作为靶向肺部感染治疗的肺部药物递送系统具有巨大潜力。
