Folic acid-functionalized chitosan nanoparticles with bioenzyme activity for the treatment of spinal cord injury.

Spinal cord injury (SCI) is a central system disease with a high rate of disability. Pathological changes such as ischemia and hypoxia of local tissues, oxidative stress and apoptosis could lead to limb pain, paralysis and even life-threatening. It was reported that catalase (CAT) was the main antioxidant in organisms, which could remove reactive oxygen species (ROS) and release oxygen (O2). However, the efficacy of the drug is largely limited due to its poor stability, low bioavailability and inability to cross the blood spinal cord barrier (BSCB). Therefore, in this study, we prepared folic acid-functionalized chitosan nanoparticles to deliver CAT (FA-CSNCAT) for solving this problem. In vivo small animal imaging results showed that FA-CSN could carry CAT across the BSCB and target to the inflammatory site. In addition, Immunofluorescence, ROS assay and JC-1 probe were used to detect the therapeutic effect of FA-CSNCAT in vitro and in vivo. The results showed that FA-CSNCAT could alleviate the hypoxic environment at the injured site and remove ROS, thereby inhibiting oxidative stress and protecting neurons, which may provide a new idea for clinical medication of SCI.

Manganese-doped albumin-gelatin composite nanogel loaded with berberine applied to the treatment of gouty arthritis in rats via a SPARC-dependent mechanism.

In this study, manganese-doped albumin-gelatin composite nanogels (MAGN) were prepared and used to load berberine (Ber) for the treatment of gouty arthritis (GA). The nanodrug delivery system (Ber-MAGN) can target inflammatory joints due to the intrinsic high affinity of albumin for SPARC, which is overexpressed at the inflammatory site of GA. Characterization of the pharmaceutical properties in vitro showed that Ber-MAGN had good dispersion, and the particle size was 121 ± 10.7 nm. The sustained release effect significantly improved the bioavailability of berberine. In vitro and in vivo experimental results showed that Ber-MAGN has better therapeutic effects in relieving oxidative stress and suppressing inflammation. Therefore, Ber-MAGN, as a potential pharmaceutical preparation for GA, provides a new reference for the clinical treatment plan of GA.

Encapsulation of Selenium Nanoparticles and Metformin in Macrophage-Derived Cell Membranes for the Treatment of Spinal Cord Injury.

Spinal cord injury is an impact-induced disabling condition. A series of pathological changes after spinal cord injury (SCI) are usually associated with oxidative stress, inflammation, and apoptosis. These pathological changes eventually lead to paralysis. The short half-life and low bioavailability of many drugs also limit the use of many drugs in SCI. In this study, we designed nanovesicles derived from macrophages encapsulating selenium nanoparticles (SeNPs) and metformin (SeNPs-Met-MVs) to be used in the treatment of SCI. These nanovesicles can cross the blood-spinal cord barrier (BSCB) and deliver SeNPs and Met to the site of injury to exert anti-inflammatory and reactive oxygen species scavenging effects. Transmission electron microscopy (TEM) images showed that the SeNPs-Met-MVs particle size was approximately 125 ± 5 nm. Drug release assays showed that Met exhibited sustained release after encapsulation by the macrophage cell membrane. The cumulative release was approximately 80% over 36 h. In vitro cellular experiments and in vivo animal experiments demonstrated that SeNPs-Met-MVs decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and reduced the expression of inflammatory (TNF-α, IL-1ß, and IL-6) and apoptotic (cleaved caspase-3) cytokines in spinal cord tissue after SCI. In addition, motor function in mice was significantly improved after SeNPs-Met-MVs treatment. Therefore, SeNPs-Met-MVs have a promising future in the treatment of SCI.

Preparation of chitosan-coated hollow tin dioxide nanoparticles and their application in improving the oral bioavailability of febuxostat.

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.

Chitosan-modified hollow manganese dioxide nanoparticles loaded with resveratrol for the treatment of spinal cord injury.

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-1ß, and Cl caspase-3) and western blot (iNOS, cox-2, IL-1ß, 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.

Codelivery of minocycline hydrochloride and dextran sulfate via bionic liposomes for the treatment of spinal cord injury.

After primary injury to the spinal cord, a series of microenvironmental changes can lead to secondary injury. The use of nano-targeted drug delivery systems to improve the postinjury microenvironment, inhibit inflammation and reduce neuronal apoptosis can be of great help during spinal cord injury (SCI) recovery. In this study, we prepared primary macrophage membranes bionic modified nanoliposomes (MH-DS@M-Lips) loaded with minocycline hydrochloride (MH) and dextran sulfate (DS) to target their delivery to the site of injury to bind calcium ions in situ and form metal ion complexes. Complex formation reduced calcium ion concentrations and calcium-associated neuronal apoptosis, while MH was slowly released to produce better anti-inflammatory effects. The successful preparation of MH-DS@M-Lips was verified using transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), western blotting and dynamic light scattering (DLS). The targeting capability of the MH-DS@M-Lips was demonstrated using a Transwell system and an in vivo imaging system. The therapeutic efficacy of MH-DS@M-Lips was examined in vitro and in vivo using flow cytometry, immunofluorescence, ELISA kits and western blotting. The results showed that SCI mice treated with MH-DS@M-Lips received high behavioral scores, which led to the conclusion that MH-DS@M-Lips have great potential for the treatment of SCI.

Siwu Granules and Erythropoietin Synergistically Ameliorated Anemia in Adenine-Induced Chronic Renal Failure Rats.

OBJECTIVE: Renal anemia in patients with end-stage chronic kidney disease is closely related to the deterioration of cardiac function, renal function, and quality of life. This study involved adenine-induced renal anemic rat models and evaluated the treatment effect of Siwu granules and/or erythropoietin (EPO). METHODS: Fifty SD rats were randomly divided into 5 groups: control, model, Siwu, EPO, and Siwu plus EPO groups. The expression levels of NO, MDA, SOD, CAT, IL-6, TNF-α, EPO, EPOR, α-SMA, and TGF-ß1 were detected in rats after 8 weeks of treatment with Siwu granules and/or EPO. RESULTS: After modeling, 47 rats entered the stage of treatment. Siwu plus EPO treatment significantly increased the rat hemoglobin content (p < 0.05) and reduced blood urea nitrogen (p < 0.05) and serum creatinine (p < 0.001). Compared with the control group, the expression of EPO and EPOR in the kidney of rats with renal failure was significantly decreased (p < 0.05). Moreover, the Siwu plus EPO group improved the level of oxidative stress in rats with chronic renal failure and reduced the expression of inflammatory factors. The expression of α-SMA and TGF-ß1 in rats with renal failure was higher, but there was no expression in the control group. CONCLUSION: Combined treatment of Siwu granules with EPO increased the expression of EPO and EPOR in the renal tissues and inhibited oxidative stress and inflammatory factors, improving the renal function and anemia.

Effect and Mechanism of ShiZhiFang on Uric Acid Metabolism in Hyperuricemic Rats.

OBJECTIVE: To explore the effect and mechanism of ShiZhiFang on uric acid metabolism. METHODS: 40 rats were divided into normal group, model group, ShiZhiFang group, and benzbromarone group. The hyperuricemic rat model was induced by yeast gavage at 15 g/kg and potassium oxonate intraperitoneal injection at 600 mg/kg for two weeks. During the next two weeks, ShiZhiFang group rats were given ShiZhiFang by gavage, and benzbromarone group rats were given benzbromarone by gavage. The serum uric acid, creatinine, blood urea nitrogen, XOD activity, urinary uric acid, urinary ß2-MG, and histopathological changes were observed in the rats of each group after treatment. RESULTS: The hyperuricemic model was established successfully and did not show the increase of serum creatinine and blood urea nitrogen. Compared with the model group, the serum uric acid, serum XOD activity, and urinary ß2-MG were significantly decreased (p < 0.05), and 24 h urinary uric acid excretion was significantly decreased (p < 0.01) in ShiZhiFang group, whereas the two treatment groups were of no statistical significant in above indicators (p > 0.05); renal histopathology showed that the lesions in two treatment groups were reduced compared to the model groups. The gene and protein expression of uric acid anion transporters rOAT1 and rOAT3 in the kidney was significantly higher than that in model group (p < 0.01). CONCLUSION: The model is suitable for the study of primary hyperuricemia. The mechanisms of ShiZhiFang on uric acid metabolism in hyperuricemic rats may be involved in reducing the activity of serum XOD and promoting the transcription and expression of rOAT1 and rOAT3 in the kidney.

Effects of Shizhifang on NLRP3 Inflammasome Activation and Renal Tubular Injury in Hyperuricemic Rats.

OBJECTIVE: Uric acid (UA) activates the NLRP3-ASC-caspase-1 axis and triggers cascade inflammatory that leads to hyperuricemic nephropathy and hyperuricemia-induced renal tubular injury. The original study aims to verify the positive effects of the traditional Chinese medicinal formula Shizhifang (SZF) on ameliorating the hyperuricemia, tubular injury, and inflammasome infiltration in the kidneys of hyperuricemic lab rats. METHOD: Twenty-eight male Sprague-Dawley rats were divided into four groups: control group, oxonic acid potassium (OA) model group, OA + SZF group, and OA + Allopurinol group. We evaluated the mediating effects of SZF on renal mitochondrial reactive oxygen species (ROS) and oxidative stress (OS) products, protein expression of NLRP3-ASC-caspase-1 axis, and downstream inflammatory factors IL-1ß and IL-18 after 7 weeks of animals feeding. RESULT: SZF alleviated OA-induced hyperuricemia and inhibited OS in hyperuricemic rats (P < 0.05). SZF effectively suppressed the expression of gene and protein of the NLRP3-ASC-caspase-1 axis through accommodating the ROS-TXNIP pathway (P < 0.05). CONCLUSION: Our data suggest that SZF alleviates renal tubular injury and inflammation infiltration by inhibiting NLRP3 inflammasome activation triggered by mitochondrial ROS in the kidneys of hyperuricemic lab rats.