Mejjo Diana Battal, Nayal Ream, Abdelwahed Wassim, Abajy Mohammad Yaser
Department of Biochemistry and Microbiology, Faculty of Pharmacy, University of Aleppo, Aleppo, Syria.
Department of Pharmacognosy, Faculty of Pharmacy, University of Aleppo, Aleppo, Syria.
Int J Nanomedicine. 2025 Sep 19;20:11525-11551. doi: 10.2147/IJN.S537934. eCollection 2025.
This research was conducted to develop an easy and safe method for synthesizing zinc oxide nanoparticles (ZnO NPs) with the aim of enhancing the efficacy and biosafety of ethanolic (CL) extract and its aqueous fraction (ACL), as a potential preclinical candidate for anti-arthritis applications.
UV-visible spectrophotometry, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy analysis, dynamic light scattering, and zeta potential were used to characterize the synthesized ZnO NPs. The optimal synthesis conditions were determined by evaluating the effects of reaction parameters. The anti-arthritis effect was investigated in vitro using albumin denaturation and human red blood cells (HRBCs) membrane stabilization tests. Additionally, Franz cells were used to determine the ex vivo permeability; carrageenan-induced paw edema, C-reactive protein measurement, and erythrocyte sedimentation rate were used to study the in vivo anti-arthritis effect. Biosafety was assessed through acute and subacute dermal toxicity tests.
Both CL and ACL could synthesize ZnO NPs with 71 and 44 nm diameters, respectively. In vitro, synthesized ZnO NPs showed superior anti-arthritis effects compared to sodium diclofenac and plant extracts, with the IC values for the albumin denaturation test being10.84 and 11.93 µg/mL for CL-ZnO NPs and ACL-ZnO NPs, respectively. The IC values for the HRBCs membrane stabilization assay were 9.74 and 14.8 µg/mL for CL-ZnO NPs and ACL-ZnO NPs, respectively. The ex vivo permeability study showed high permeability (946.8 µg/h/cm²). In vivo, both synthesized ZnO NPs demonstrated significant inhibition of carrageenan-induced edema, and performed better than sodium diclofenac and plant extracts, with maximum inhibition of 85.96±14.21% (CL-ZnO NPs) and 92.97±6.43% (ACL-ZnO NPs). Acute and subacute toxicity evaluations revealed no adverse effects.
The green synthesized ZnO NPs from both CL and ACL had high permeability, superior efficacy, and biosafe which make them a promising natural product for managing arthritis conditions.
本研究旨在开发一种简便、安全的合成氧化锌纳米颗粒（ZnO NPs）的方法，以提高乙醇提取物（CL）及其水相部分（ACL）作为抗关节炎潜在临床前候选药物的疗效和生物安全性。
采用紫外可见分光光度法、傅里叶变换红外光谱法、场发射扫描电子显微镜、能量色散X射线光谱分析、动态光散射和zeta电位对合成的ZnO NPs进行表征。通过评估反应参数的影响来确定最佳合成条件。使用白蛋白变性和人红细胞（HRBCs）膜稳定试验在体外研究抗关节炎作用。此外，使用Franz扩散池测定离体渗透性；角叉菜胶诱导的爪肿胀、C反应蛋白测量和红细胞沉降率用于研究体内抗关节炎作用。通过急性和亚急性皮肤毒性试验评估生物安全性。
CL和ACL均可分别合成直径为71和44 nm的ZnO NPs。在体外，合成的ZnO NPs与双氯芬酸钠和植物提取物相比显示出优异的抗关节炎作用，CL-ZnO NPs和ACL-ZnO NPs在白蛋白变性试验中的IC值分别为10.84和11.93 μg/mL。CL-ZnO NPs和ACL-ZnO NPs在HRBCs膜稳定试验中的IC值分别为9.74和14.8 μg/mL。离体渗透性研究显示出高渗透性（946.8 μg/h/cm²）。在体内，两种合成的ZnO NPs均显示出对角叉菜胶诱导的水肿有显著抑制作用，且比双氯芬酸钠和植物提取物表现更好，最大抑制率分别为85.96±14.21%（CL-ZnO NPs）和92.97±6.43%（ACL-ZnO NPs）。急性和亚急性毒性评估未发现不良反应。
由CL和ACL绿色合成的ZnO NPs具有高渗透性、优异的疗效和生物安全性，使其成为治疗关节炎的有前景的天然产物。
