Journal of Materials Chemistry B
·
2023
·
IF 7
Zeng Yi,Yaqin Ran,Xiangyu Chen,Qiulan Tong,Lei Ma,Yunfei Tan,Xiaomin Ma,Xudong Li
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial inflammation, cartilage damage and bone erosion. In the progression of RA, the inflammatory mediators including ROS, NO, TNF-α, and IL-6 play important roles in the aggravation of inflammation. Hence, reducing the generation and release of inflammatory mediators is of great importance. However, the high dose and frequent administration of clinical anti-inflammatory drugs such as glucocorticoids (GCs) usually lead to severe side effects. The development of nanotechnology provides a promising strategy to overcome these issues. Here, polyphenol-based nanoparticles with inherent anti-oxidative and anti-inflammatory activities were developed and used as a kind of nanocarrier to deliver dexamethasone (Dex). The in vitro experiments confirmed that the nanoparticles and drugs could act synergistically for suppressing inflammatory mediators in the LPS/INF-γ-induced inflammatory cell model. After intravenous administration, the Dex-loaded nanoparticles with good biosafety showed effective accumulation in inflamed joints and improved therapeutic efficacy by inducing anesis of synovial inflammation and cartilage destruction over free Dex in a collagen-induced arthritis (CIA) mouse model. The results demonstrated that polyphenol-based nanoparticles with therapeutic functions may serve as an innovative platform to synergize with chemotherapeutic agents for enhanced treatment of inflammatory diseases.
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高影响因子
TOXICOLOGY LETTERS
·
2022
·
IF 4.271
Mingyang Chen,Mengru Bai,Yaodong Yi,Shuanghui Lu,Jun Luo,Ping Li,Hengbin Zhang,Huidi Jiang,Hui Zhou
Glucocorticoids such as dexamethasone (DEX) are widely prescribed to treat numerous conditions and diseases. However, glucocorticoid-induced liver lipid metabolism disorder, even nonalcoholic fatty liver disease , has caused extensive attention. Since fatty acid transporters such as CD36 and FATP play crucial roles in hepatic fatty acid uptake, this work examined their potential involvement in DEX-induced liver lipid accumulation. Chronic DEX administration (1–5 mg/kg/day over 28 days) induced hepatic lipid accumulation in mice. Fatty acid uptake in HepG2 cells and mouse primary hepatocytes was also stimulated after incubation with 0.5–2 μM DEX. Meanwhile, qPCR and western blotting demonstrated dose-dependent upregulation of CD36 expression by DEX in the mouse liver and in cultured hepatocytes. Glucocorticoid receptor (GR) inhibition with mifepristone (RU486) and siRNA-mediated GR knockdown attenuated lipid accumulation in hepatocytes by inhibiting DEX-induced CD36 upregulation, and direct binding of GR to the CD36 promoter was demonstrated by luciferase reporter and chromatin immunoprecipitation assays. These results indicate that DEX promotes free fatty acid uptake leading to hepatic steatosis by upregulating CD36 expression via activation of GR. Thus, strategies aimed at inhibiting GR/CD36 expression or activity might help prevent or reduce the onset and progression of hepatic lipid metabolism disorders induced by glucocorticoid drugs.
研究领域:
药理学
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肝病学
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分子生物学
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高影响因子
Food Bioscience
·
2026
·
IF 6.2
Haiwang Liu,Zhongyan Bao,Yu Gao,Fengqin Feng,Minjie Zhao,Qing Lv,Qian Yang,Xi Zhang
Drug-induced malnutrition resulting from long-term glucocorticoid therapy has increasingly become a clinical concern. Dietary-derived active peptides represent an effective nutritional intervention strategy, yet the specific mechanisms of action of albumin peptides (AP) remain unclear. This study systematically evaluated the therapeutic effects of AP in a Dexamethasone (DEX)-induced malnutrition mouse model and elucidated its mechanisms through integrated analyses of liver transcriptomics, non-targeted metabolomics, and quantitative fatty acid profiling. Results demonstrated that AP administration ameliorated DEX-induced protein catabolism, increased serum prealbumin (PAB) levels by 183.66%, elevated total protein (TP) levels by 14.6%, and significantly reversed hepatic steatosis and gastrocnemius muscle degeneration. Transcriptomic analysis revealed that peroxisome proliferator-activated receptor alpha (PPARα) was the primary signaling pathway affected by AP, with gene expression levels of Ppara and related genes restored to normal ranges. Non-targeted metabolomic analyses further identified correlations between this transcriptional response and prostaglandin, leukotriene, and diacylglycerol levels. Fatty acid quantification showed that AP restored hepatic arachidonic acid levels by 17.3%. Correlation analyses revealed a significant positive relationship between hepatic arachidonic acid levels and PPARα expression (R≥0.97), reinforcing the hypothesis that arachidonic acid serves as a key endogenous ligand mediating the interaction between AP and PPARα. Additionally, AP restored short-chain fatty acid concentrations in feces, indicating the pivotal role of the gut-liver axis in phenotypic development. Together, these findings suggest that AP alleviates DEX-induced malnutrition partly through restoration of hepatic arachidonic acid metabolism and reactivation of PPARα signaling, supporting its potential as a functional food ingredient for drug-induced malnutrition.
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Journal of Radiation Research and Applied Sciences
·
2025
·
IF 2.5
Lan Tang,Xin Zhang,Ye Huang,Depeng Kong,Yiwen Yan,Zhimin Ou,Mulan Zhu,Yi Li,Jianwei Wang
Objective This study aimed to enhance the solubility and dispersion of poorly water-soluble dexamethasone (DEX) in oral films by developing a novel pullulan-vitamin E succinate (PUL-VES) coupling compound (designated PUVS3) as the film matrix. Methods The amphiphilic coupling compound PUVS3 was synthesized, characterized and evaluated. Using PUVS3 as a solubilizing/suspension agent, and PUL as the film-forming material, a dexamethasone-fast dissolving oral film (DEX-FDOF) was prepared by solvent casting method. The film was evaluated for appearance, microstructure, mechanical properties, weight variation, content uniformity, disintegration time and in vitro dissolution. Results The DEX-FDOF formulation exhibited a smooth surface with no observable drug precipitation and demonstrated excellent transparency. Both weight variation and content uniformity complied with the pharmacopoeial standards. The film displayed rapid disintegration (<15s) and favorable mechanical properties with an elastic modulus of 35–45 MPa and elongation at break of 17%–20%. Notably, in vitro dissolution reached approximately 47 % within 10 min, representing a significant improvement over the pure drug. This enhancement was achieved through the use of a self-synthesized PUL-VES coupling compound as the film matrix. This innovative approach enabled homogeneous dispersion of the poorly water-soluble DEX within the water-soluble oral film while simultaneously improving its solubility characteristics. Conclusion The DEX-FDOF, fabricated using the self-synthesized PUL-VES coupling compound as the matrix, exhibited excellent uniformity, mechanical strength, rapid disintegration (<15 s), and notably enhanced dissolution (47 % in 10 min), demonstrating its potential as an effective delivery system for poorly soluble drugs such as DEX.
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Biointerphases
·
2024
·Vol. 19
·期 2
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IF 1.6
Chen Danfei,Xuan Xiaobo,Chen Yuyan,Fang Xia,Liu Liwei,Wang Guowei,Chen Jian
Allergic asthma (AA) is a common breathing disorder clinically characterized by the high occurrence of acute and continuous inflammation. However, the current treatment options for AA are lacking in effectiveness and diversity. In this study, we determined that the cell membrane receptor of gamma-glutamyl transferase (GGT) was highly overexpressed on the inflammatory cells that infiltrate the pulmonary tissues in AA cases. Therefore, we developed a GGT-specific dendrimer-dexamethasone conjugate (GSHDDC) that could be administered via aerosol inhalation to treat AA in a rapid and sustained manner. The GSHDDC was fabricated by the covalent attachment of 6-hydroxyhexyl acrylate-modified dexamethasone to polyamidoamine dendrimers via a carbonic ester linkage and the amino Michael addition, followed by the surface modification of the dendrimers with the GGT substrate of glutathione. After aerosol inhalation by the AA mice, the small particle-sized GSHDDC could easily diffuse into pulmonary alveoli and touch with the inflammatory cells via the glutathione ligand/GGT receptor-mediated recognition. The overexpressed GGT on the surface of inflammatory cells then triggers the gamma-glutamyl transfer reactions of glutathione to generate positively charged primary amines, thereby inducing rapid cationization-mediated cellular endocytosis into the inflammatory cells. The dexamethasone was gradually released by the intracellular enzyme hydrolysis, enabling sustained anti-inflammatory effects (e.g., reducing eosinophil infiltration, decreasing the levels of inflammatory factors) in the ovalbumin-induced AA mice. This study demonstrates the effectiveness of an inhalational and active inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient AA therapy.
研究领域:
药理学
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肺科学
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纳米医学
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免疫学
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高影响因子
MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Ying Zhao,Changhao Jia,Zhixin Yao,Gang Chen,Gui Huang,Hui Li,Linghong Lu,Taiwei Jin,Yan Tang,Zengyan Zhu,Xuenong Zhang
Folic acid (FA) has been widely engineered to promote the targeted delivery of FA-modified nanoparticles (NPs) by recognizing the folate receptor α (FRα). However, the efficacy of FA-targeted therapy significantly varied with the abundance of FRα and natural immunoglobulin levels in different tumors. Therefore, a sequential therapy of dexamethasone (Dex)-induced FRα amplification and immunosuppression combined with FA-functionalized doxorubicin (DOX) micelles to synergistically suppress tumor proliferation was proposed in this study. In brief, a pH/reduction-responsive FA-functionalized micelle (FCSD) was obtained by grafting FA, derivatization-modified cholesterol, and 2,3-dimethylmaleic anhydride onto a chitosan oligosaccharide. The obtained FCSD/DOX NPs can effectively deliver DOX in tumors, and their targeting efficiency can be further improved with Dex pretreatment to decrease the immunoglobulin M (IgM) content in serum and amplify FRα levels on the surface of M109 cells. After internalization, charge reversal and disulfide bond breakage of FCSD vectors under the stimulation of tumor extracellular pH (pHe) and intracellular glutathione (GSH) would contribute to the disintegration of vectors and the rapid release of DOX. The sequential therapy that combined Dex pretreatment and targeted chemotherapy by FCSD/DOX NPs demonstrated superior tumor suppression compared with monotherapy, which is expected to provide a potential strategy for FRα-positive lung cancer patients.
研究领域:
药学
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癌症研究
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纳米技术
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生物医学工程
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Contrast Media & Molecular Imaging
·
2022
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IF 3.009
Wenjie Cheng,Yushan Song,Yanfang Liu,Xiaohua Sun,Wanlu Ren
To assess the preventive role of dexamethasone (Dex) in the development of neuroinflammation and concomitant neurocognitive disorders following acute inflammation. C57BL6 mice were fallen into the sham group, ischemia-reperfusion (I/R) group, and I/R + Dex group randomly. In the end, behavioral alterations were assessed with the Morris water maze (MWM) test, passive avoidance test (PAT), and open field test (OFT). The serum levels of IL-1β and TNF-α were detected by ELISA. Immunofluorescence was adopted to observe the NF-kB expression in the hippocampus. In addition, TLR4, NF-kB, CD68, and CD206 were examined by Western blot. The cognitive ability of mice can be impaired by tourniquet-induced acute inflammation, and these changes were prevented by Dex. Compared to the I/R group, Dex pretreatment could decrease levels of IL-1β and TNF-α proteins in serum. Besides, Dex preconditioning significantly decreased the utterance of NF-kB immunoreactive cells and TLR4, NF-kB, and CD68 overexpression in the hippocampus. Dex partly through inhibiting microglia transformation to the M1 polarization state and inactivating the TLR4/NF-kB pathway attenuates the cognitive disorders in mice.
研究领域:
神经科学
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免疫学
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药理学
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
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IF 3.997
Renshu Zhang,Lei Lei,Qianqian Song,Xingyi Li
Combining a low-molecular-weight hydrogel (LMWH) with a polymeric hydrogel overcomes the disadvantages of the LMWH ( e.g. , its low mechanical property) and is associated with the enhancement of materials performance, which is useful in a variety of biomedical applications. In the present work, a hybrid hydrogel that combines dexamethasone sodium phosphate (Dexp) and a polysaccharide (alginate) was explored via a calcium ion coordination strategy. With the addition of Ca 2+ to an aqueous solution of Dexp/alginate, the Ca 2+ /Dexp/alginate hybrid hydrogel formed spontaneously. The formed Ca 2+ /Dexp/alginate hybrid hydrogels were thoroughly characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). An in vitro drug release study indicated that the formed Ca 2+ /Dexp/alginate hybrid hydrogel provided a slower drug release rate than did the Ca 2+ /Dexp hydrogel, and the drug release behaviour could be finely tailored by the change of Ca 2+ concentration. More importantly, the subcutaneous injection of the Ca 2+ /Dexp/alginate hybrid hydrogel significantly extended the in vivo retention of the hydrogel in situ compared to that of the Ca 2+ /Dexp hydrogel. The in vivo pharmacokinetic analysis indicated that the Ca 2+ /Dexp/alginate hybrid hydrogel could greatly extend drug release in vivo and significantly improve drug bioavailability compared to the Ca 2+ /Dexp hydrogel. As such, the formed Ca 2+ /Dexp/alginate hybrid hydrogel combined the greater resilience of an alginate network with the long in vivo duration of a low-molecular-weight hydrogel (Ca 2+ /Dexp hydrogel) and remarkably enhanced drug bioavailability, which might open an avenue for the design of self-assembling steroidal drug-polysaccharide hybrid hydrogels for drug delivery applications.
研究领域:
生物材料学
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药剂学
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PubMed
高影响因子
Drug Design Development and Therapy
·
2022
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IF 4.319
Liang Wang,Qiushi Li,Haibo Yan,Guangjun Jiao,Hongliang Wang,Hai Chi,Hongming Zhou,Lu Chen,Yu Shan,Yunzhen Chen
Purpose Glucocorticoids are used for the treatment of inflammatory diseases, but glucocorticoid treatment is associated with bone damage. Resveratrol is a phytoalexin found in many plants, and we investigated its protective role on dexamethasone-induced dysfunction in MC3T3-E1 cells and primary osteoblasts.Materials and Methods MC3T3-E1 cells and primary osteoblasts were treated with dexamethasone in the presence/absence of different doses of resveratrol for 24 or 48 h. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium (MTT) and lactate dehydrogenase (LDH) assays were used to evaluate cell viability. Apoptosis was analyzed by a flow cytometry. An alkaline phosphatase (ALP) activity assay and Alizarin Red S staining were used to study osteoblast differentiation. Expression of osteoblast-related genes was measured by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The AMP-activated protein kinase (AMPK) signaling pathway and mitochondrial expression of superoxide dismutase were evaluated by Western blotting. Intracellular reactive oxygen species (ROS), adenosine triphosphate (ATP) content, mitochondrial-complex activity, and mitochondrial DNA content were measured to evaluate mitochondrial function.Results Resveratrol induced the proliferation and inhibited apoptosis of osteoblasts in the presence of dexamethasone. Resveratrol increased the ALP activity and mineralization of osteoblasts. Resveratrol also attenuated dexamethasone-induced inhibition of mRNA expression of osteogenesis maker genes, including bone morphogenetic protein-2, osteoprotegerin, runt-related transcription factor-2, and bone Gla protein. Resveratrol alleviated dexamethasone-induced mitochondrial dysfunction. Resveratrol strongly stimulated expression of peroxisome proliferator–activated receptor-γ coactivator 1α and sirtuin-3 genes, as well as their downstream target gene superoxide dismutase-2. Resveratrol induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). Blockade of AMPK signaling using compound C reversed the protective effects of resveratrol against dexamethasone.Conclusion Resveratrol showed protective effects against dexamethasone-induced dysfunction of osteoblasts by activating AMPK signaling.
研究领域:
药理学
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细胞生物学
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分子生物学
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骨骼健康
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高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2018
·Vol. 41
·期 11
·2441-2452
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IF 2.415
Wei Du,Bilin Zhang,Pengqi Guo,Guoning Chen,Chun Chang,Qiang Fu
Dexamethasone-imprinted polymers were fabricated by reversible addition–fragmentation chain transfer polymerization on the surface of magnetic nanoparticles under mild polymerization conditions, which exhibited a narrow polydispersity and high selectivity for dexamethasone extraction. The dexamethasone-imprinted polymers were characterized by scanning electron microscopy, transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive spectrometry, and vibrating sample magnetometry. The adsorption performance was evaluated by static adsorption, kinetic adsorption and selectivity tests. The results confirmed the successful construction of an imprinted polymer layer on the surface of the magnetic nanoparticles, which benefits the characteristics of high adsorption capacity, fast mass transfer, specific molecular recognition, and simple magnetic separation. Combined with high-performance liquid chromatography, molecularly imprinted polymers as magnetic extraction sorbents were used for the rapid and selective extraction and determination of dexamethasone in skincare cosmetic samples, with the accuracies of the spiked samples ranging from 93.8 to 97.6%. The relative standard deviations were less than 2.7%. The limit of detection and limit of quantification were 0.05 and 0.20 μg/mL, respectively. The developed method was simple, fast and highly selective and could be a promising method for dexamethasone monitoring in cosmetic products.
研究领域:
分析化学
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材料科学
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药物分析
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PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Guang-rong Lu,Rui-zhen Wang,Xin-yu Zhao,Jun-er Xu,Cheng-ke Huang,Wei Sun,Rui-jie Chen,Zhe Wang
Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC (0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC (0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.
研究领域:
药理学
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肿瘤学
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临床医学
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PubMed
高影响因子
Applied Materials Today
·
2024
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IF 7.2
Yaru Yue,Zhengquan Liao,Yingqian Zhou,Yongteng Zhang,Zeshu Wang,Shengtao Wang,Xianglong Hu,Quan Zhou
Rheumatoid arthritis (RA) is a common autoimmune disease, and the abnormal proliferation of fibroblast-like synoviocytes (FLSs) in inflamed joints plays a key role in the pathogenesis of RA, which has become an important therapeutic target for RA treatment. This work reported a facilely formulated nanoparticle from saponin (Sap) and dexamethasone (Dex) in precise ratio, affording the resultant Dex@Sap nanoparticles. Benefiting from the enlargement of vascular endothelial cell gap at the inflammation site and intra-articular injection, Dex@Sap could accumulate at the inflamed joints to inhibit excessive proliferation of FLSs and mediate cell apoptosis, achieving symptomatic relief and efficient RA treatment, while reducing the amount of drug needed as well as the occurrence of adverse reactions. Typical AKT (also known as protein kinase B, PKB)/mTOR (mammalian target of rapamycin) pathway was observed to be inhibited, and the mitochondria-mediated intracellular reactive oxygen species (ROS) level was also upregulated by Dex@Sap. Further in vivo evaluations demonstrated that Dex@Sap could significantly alleviate RA-induced inflammatory response and the expression of pro-inflammatory cytokines to cure joint damage in collagen-induced arthritis mice and rats. This work provides a clinically promising nanomedicine to synergistically treat RA.
研究领域:
药理学
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免疫学
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纳米技术
·
风湿病学
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高影响因子
危险品化学品经营许可证（带存储）