ABSTRACT
Inflammatory environments provide vital biochemical stimuli (i.e., oxidative stress, pH, and enzymes) for triggered drug delivery in a controlled manner. Inflammation alters the local pH within the affected tissues. As a result, pH-sensitive nanomaterials can be used to effectively target drugs to the site of inflammation. Herein, we designed pH-sensitive nanoparticles in which resveratrol (an anti-inflammatory and antioxidant compound (RES)) and urocanic acid (UA) were complexed with a pH-sensitive moiety using an emulsion method. These RES-UA NPs were characterized by transmission electron microscopy, dynamic light scattering, zeta potential, and FT-IR spectroscopy. The anti-inflammatory and antioxidant activities of the RES-UA NPs were assessed in RAW 264.7 macrophages. The NPs were circular in shape and ranged in size from 106 to 180 nm. The RES-UA NPs suppressed the mRNA expression of the pro-inflammatory molecules inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Incubation of LPS-stimulated macrophages with RES-UA NPs reduced the generation of reactive oxygen species (ROS) in a concentration-dependent manner. These results suggest that pH-responsive RES-UA NPs can be used to decrease ROS generation and inflammation.
Subject(s)
Anti-Inflammatory Agents , Antioxidants , Nanoparticles , Resveratrol , Urocanic Acid , Humans , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Cyclooxygenase 2/metabolism , Hydrogen-Ion Concentration , Inflammation/metabolism , Lipopolysaccharides , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Reactive Oxygen Species/metabolism , Resveratrol/chemistry , Resveratrol/pharmacology , Spectroscopy, Fourier Transform Infrared , Tumor Necrosis Factor-alpha/metabolism , Urocanic Acid/chemistry , Urocanic Acid/pharmacologyABSTRACT
In the current study, we fabricated tannic acid-alendronate (TA-ALN) nanocomplexes (NPXs) via self-assembly. These TA-ALNs were characterized by dynamic light scattering, zeta potential, transmission electron microscopy, and FT-IR spectroscopy. The TA-ALNs were evaluated for antioxidant, anti-inflammatory, and osteogenesis-accelerating abilities in osteoblast-like cells (MC3T3-E1 cells). All TA-ALNs displayed nano-sized beads that were circular in form. Treatment with TA-ALN (1:0.1) efficiently removed reactive oxygen species in cells and protected osteoblast-like cells from toxic hydrogen peroxide conditions. Moreover, TA-ALN (1:0.1) could markedly decrease the mRNA levels of pro-inflammatory mediators in lipopolysaccharide-stimulated cells. Furthermore, cells treated with TA-ALN (1:1) exhibited not only significantly greater alkaline phosphatase activity and calcium collection, but also outstandingly higher mRNA levels of osteogenesis-related elements such as collagen type I and osteocalcin. These outcomes indicate that the prepared TA-ALNs are excellent for antioxidant, anti-inflammatory, and osteogenic acceleration. Accordingly, TA-ALN can be used latently for bone renovation and regeneration in people with bone fractures, diseases, or disorders.