Biotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Medical Nanotechnology, School of Advanced Medical Science and Technology, Shiraz University of Medical Sciences, Shiraz, Iran; Guilan Road Trauma Research Center, Guilan University of Medical Sciences, Rasht, Iran.
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Int J Biol Macromol. 2024 Apr;265(Pt 2):130654. doi: 10.1016/j.ijbiomac.2024.130654. Epub 2024 Mar 29.
Trinitroglycerin (TNG) is a remarkable NO-releasing agent. Here, we synthesized TNG based on chitosan Nanogels (Ngs) for ameliorating complications associated with high-dose TNG administration.
TNG-Ngs fabricated through ionic-gelation technique. Fourier-transformed infrared (FT-IR), zeta-potential, dynamic light scattering (DLS), and electron microscopy techniques evaluated the physicochemical properties of TNG-Ngs. MTT was used to assess the biocompatibility of TNG-Ngs, as the antioxidative properties were determined via lactate dehydrogenase (LDH), reactive oxygen species (ROS), and lipid peroxide (LPO) assays. The antibacterial activity was evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE).
Physicochemical characterization reveals that TNG-Ngs with size diameter (96.2 ± 29 nm), polydispersity index (PDI, 0.732), and negative zeta potential (-1.1 mv) were fabricated. The encapsulation efficacy (EE) and loading capacity (LC) were obtained at 71.1 % and 2.3 %, respectively, with no considerable effect on particle size and morphology. The cytotoxicity assay demonstrated that HepG2 cells exposed to TNG-Ngs showed relative cell viability (RCV) of >80 % for 70 μg/ml compared to the TNG-free drug at the same concentration (P < 0.05). TNG-Ngs showed significant differences with the TNG-free drug for LDH, LPO, and ROS formation at the same concentration (P < 0.001). The antibacterial activity of the TNG-Ngs against S. aureus, E. coli, VRE, and MRSA was higher than the TNG-free drug and Ngs (P < 0.05).
TNG-Ngs with enhanced antibacterial and antioxidative activity and no obvious cytotoxicity might be afforded as novel nanoformulation for promoting NO-dependent diseases.
三硝酸甘油酯（TNG）是一种显著的一氧化氮释放剂。在这里，我们基于壳聚糖纳米凝胶（Ngs）合成了 TNG，以改善与高剂量 TNG 给药相关的并发症。
通过离子凝胶技术制备 TNG-Ngs。傅里叶变换红外（FT-IR）、Zeta 电位、动态光散射（DLS）和电子显微镜技术评估了 TNG-Ngs 的物理化学性质。MTT 用于评估 TNG-Ngs 的生物相容性，通过乳酸脱氢酶（LDH）、活性氧（ROS）和脂质过氧化物（LPO）测定来确定其抗氧化性能。评估了 TNG-Ngs 对金黄色葡萄球菌（S. aureus）、大肠杆菌（E. coli）、耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）的抗菌活性。
物理化学特性表明，制备了粒径（96.2 ± 29 nm）、多分散指数（PDI，0.732）和负 Zeta 电位（-1.1 mv）的 TNG-Ngs。包封效率（EE）和载药量（LC）分别为 71.1%和 2.3%，对粒径和形态没有明显影响。细胞毒性试验表明，与相同浓度的无 TNG 药物相比，暴露于 TNG-Ngs 的 HepG2 细胞的相对细胞活力（RCV）>80%，达到 70μg/ml（P<0.05）。TNG-Ngs 在相同浓度下与无 TNG 药物相比，LDH、LPO 和 ROS 形成有显著差异（P<0.001）。TNG-Ngs 对金黄色葡萄球菌、大肠杆菌、万古霉素肠球菌和耐甲氧西林金黄色葡萄球菌的抗菌活性高于无 TNG 药物和 Ngs（P<0.05）。
具有增强的抗菌和抗氧化活性且无明显细胞毒性的 TNG-Ngs 可能作为促进一氧化氮依赖性疾病的新型纳米制剂。
