Search

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses, and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum–gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum–gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1β, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA. Graphical Abstract

The aim of this study was to design a chitosan-coated hollow tin dioxide nanosphere (CS-HSn) for loading febuxostat (FEB) using an adsorption method to obtain a sustained-release system (CS-HSn-FEB) to improve the oral bioavailability of FEB. The morphological characteristics of hollow tin dioxide nanospheres (HSn) and CS-HSn were analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The hemolysis test and CCK-8 test were used to assess the biosafety of HSn and CS-HSn. Powder X-ray diffraction (PXRD) and differential scanning thermal analysis (DSC) were performed on CS-HSn-FEB to analyze the drug presence status. The dissolution behavior and changes in plasma drug concentration of CS-HSn-FEB were evaluated in vitro and in vivo. Sections of intestinal tissues from SD rats were obtained to observe whether chitosan could increase the distribution of nanoparticles in the intestinal tissues. The results showed that FEB was present in CS-HSn in an amorphous state. Moreover, CS-HSn, with good biosafety, significantly improved the water solubility and oral absorption of FEB, indicating that CS-HSn has great potential to improve the intestinal absorption and oral bioavailability of insoluble drugs.

Spinal cord injury (SCI) is a serious central nervous system disease, and secondary injury, including oxidative stress, the inflammatory response and accompanying neuronal apoptosis, will aggravate the condition. Due to the existence of the blood–spinal cord barrier (BSCB), the existing drugs for SCI treatment are difficulty to reach the injury site and thus their efficacy is limited. In this study, we designed chitosan-modified hollow manganese dioxide nanoparticles (CM) for the delivery of resveratrol to help it pass through the BSCB. Resveratrol (Res), a poorly soluble drug, was adsorbed into CM with a particle size of approximately 130 nm via the adsorption method, and the drug loading reached 21.39 ± 2.53%. In vitro dissolution experiment, the Res release of the loaded sample (CMR) showed slowly release behavior and reached about 87% at 36 h. In vitro at the cellular level and in vivo at the animal level experiments demonstrated that CMR could alleviate significantly oxidative stress by reducing level of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and increasing glutathione peroxidase (GSH) level. Additionally, immunofluorescence (iNOS, IL-1β, and Cl caspase-3) and western blot (iNOS, cox-2, IL-1β, IL-10, Cl caspase-3, bax, and bcl-2) were used to detect the expression of related factors, which verified that CMR could also reduce inflammation and neuronal apoptosis. These results indicated that CM, as a potential central nervous system drug delivery material, was suitable for SCI treatment.

In the actual soil environment, due to the unpredictable characteristics of metal pitting corrosion. Therefore, in this study, soil composed of different concentrations of corrosion medium was used for the mental corrosion test, and the experimental results of single ion and multiple ions were compared. At the same time, the corrosion behavior of metals is introduced in combination with the mathematical model of unsteady diffusion. In addition, the cellular automata model verification method is used to study the comparison and verification of the diffusion growth model of the model corrosion pit in different iteration steps under the discrete mathematical model. The results show that the growth and diffusion trend of corrosion pits controlled by the concentration of SO42-, HCO3–, and Cl- is consistent basically with the law reflected by cellular automata.

Abstract Background Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI. Results By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs−cl−NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs−cl−NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs−cl−NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage. Conclusions A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI. Graphical Abstract

Stroke is a central nervous system disease with a high incidence at present. It can cause pathological changes such as oxidative stress, inflammation, neuronal apoptosis, and lead to disturbance of consciousness, disability, and even death. Due to the existence of the blood-brain barrier (BBB), most of the drugs cannot reach the lesions and exert their efficacy fully. Therefore, the purpose of this research was to design a lactoferrin functionalized hollow mesoporous manganese doped silica nanoparticles (LHMMSN) for delivery of insoluble drug resveratrol (RES). The system could help insoluble drugs pass through the BBB and target inflammatory sites to exert the antioxidant stress, anti-inflammatory and neuroprotective effects. The RES was adsorbed into LHMMSN with a particle size of about 140 nm by adsorption method, and the drug loading reached 39.32 ± 2.46%. In vitro and in vivo experiments showed that LHMMSN-RES could increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce brain reactive oxygen species (ROS) and malondialdehyde (MDA) content, increase the expression of anti-inflammatory factors (IL-10) and anti-apoptotic factors (bcl-2) in brain tissue, and reduce brain tissue pro-inflammatory factors (TNF-α, IL-1β, IL-6) and pro-apoptotic factors (BAX, Cleaved caspase-3) expression. In summary, LHMMSN-RES can reduce inflammation and protect nerve cells by inhibiting oxidative stress, thereby promoting the recovery of motor function in middle cerebral artery occlusion (MCAO) model rats.

The objective of this study was to prepare Herceptin-functionalized SK-BR-3 cell membrane-wrapped paclitaxel nanocrystals (HCNCs) as a targeted delivery module for HER2-positive breast cancer. According to transmission electron microscopy (TEM) images, HCNCs presented a membrane-coated cubic shape with a particle size of approximately 220 nm. In vitro release test suggested that HCNCs had a certain sustained release effect of paclitaxel (PTX). Cell uptake experiments, in vivo imaging, and tissue distribution experiments demonstrated that HCNCs had excellent targeting ability to homologous tumor cells (SK-BR-3). The results of MTT, flow cytometry, Western blot, cell immunofluorescence staining, and in vivo antitumor experiments proved that HCNCs had a more significant ability to promote HER2-positive breast cancer cell apoptosis and inhibit its proliferation. These results clearly concluded that HCNCs were a promising nano-targeted preparation in anti-HER2-positive breast cancer.