APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING
·
2016
·Vol. 122
·期 7
·1-8
·
IF 1.444
Sun Huanghui,Zhang Lingfan,Xia Wei,Chen Linxiao,Xu Zhizhen,Zhang Wenqing
Functionalized graphene oxide with its unique physical and chemical properties is widely applied in biomaterials, especially in drug carrier materials. In the past few years, a number of different drugs have been loaded on functionalized graphene oxide via π–π stacking and hydrophobic interactions. The present report described a new approach, dexamethasone phosphate successfully loaded onto graphene oxide–chitosan nanocomposites as drug carrier materials by covalent bonding of phosphate ester linkage. Compared with the graphene oxide–chitosan nanocomposites that dexamethasone phosphate was loaded on via simple physical attachment, covalently linked composites as drug carrier materials were more biocompatible which effectively reduced the burst release of drug, and controlled the release of drug in different pH conditions.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
DOI
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Jiawei Li,Pengyue Liu,Yue Zhang,Fan Yang
Allergic conjunctivitis is a common ocular surface condition. Although corticosteroids are potent anti-inflammatory agents for its management, their use is often restricted by potential side effects. Conventional eye drops face challenges such as short retention time and poor corneal permeability, resulting in low drug bioavailability. To overcome these limitations, we developed a preservative-free synthetic high-density lipoprotein (sHDL) nanodisc eye drop containing dexamethasone palmitate. This novel formulation enhances drug stability and extends retention time on the ocular surface. In a mouse model of ovalbumin (OVA)-induced allergic conjunctivitis, the nanodisc eye drop significantly alleviated symptoms while reducing corticosteroid concentration, demonstrating excellent safety and biocompatibility. This innovative approach shows great promise for the treatment of allergic conjunctivitis and may lay the groundwork for new therapeutic strategies in anterior ocular disease management.
研究领域:
眼科
·
药物递送系统
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
GENERAL AND COMPARATIVE ENDOCRINOLOGY
·
2018
·
IF 2.564
Xixi Song,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Hai Lin
Ghrelin is one of the most important appetite regulating peptides, involved in the regulation of energy homeostasis. The role of ghrelin on the appetite and fat metabolism in chickens is different from that of ghrelin in mammals. Glucocorticoids and insulin are important hormones and work differently in energy regulation of body. In this study, the effects of dexamethasone (DEX, 2.0 mg/kg BW), subcutaneous insulin injection (40 µg/kg BW), and glucose load on ghrelin secretion and expression were determined in broilers. DEX treatment increased circulating ghrelin concentration in broiler fed with either a low-energy diet (11.05 MJ/kg of metabolizable energy) or a high-energy diet (14.44 MJ/kg of metabolizable energy). The expression levels of ghrelin were increased while both ghrelin and its receptor GHS-R1a expression levels were stimulated by DEX. A single subcutaneous insulin injection (40 µg/kg BW) or oral glucose infusion (2 g/kg BW) rise circulating ghrelin level. Ghrelin expression in the proventriculus was increased by insulin treatment but unchanged by glucose load. DEX had no detectable influence on ghrelin and GHS-R1a expression in the hypohtalamus, whereas insulin suppressed their expression. In conclusion, both insulin and glucocorticoid stimulate ghrelin secretion in chickens, in contrast to mammals. Glucocorticoids evoke peripheral ghrelin/GHS-R1a system while insulin increases peripheral ghrelin expression and suppress the activation of central ghrelin/GHS-R1a system. The result suggests that ghrelin involved in the modulating network of energy homeostasis in concert with glucocorticoids and insulin.
研究领域:
动物科学
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内分泌学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Rong Chen,Xiangrong Dai,Rongjiao Sun,Yi Liao,Jiajia Dong,Ying Tan,Xuru Jin
Acute Lung Injury (ALI) is a clinical syndrome associated with various respiratory diseases and injuries. While inhalable drug delivery systems offer the advantage of direct pulmonary targeting and reduced systemic toxicity, their therapeutic efficacy is frequently compromised by the tracheobronchial mucus barrier. To address this limitation, we developed PCL-ss-PSBMA, a novel nanocarrier engineered to overcome the constraints of conventional micelle platforms, which typically depend on either hydrophilic coatings or single-response mechanisms. By integrating zwitterionic groups and disulfide bonds in a dual-functional design, PCL-ss-PSBMA achieves synergistic optimization of mucus barrier penetration and glutathione (GSH)-triggered drug release. In addition, the nanocarrier also exhibits excellent biocompatibility, further ensuring its safety in therapeutic applications. In an ALI murine model, PCL-ss-PSBMA@DEX markedly improved the delivery efficiency and utilization rate of dexamethasone (DEX) through its dual mechanisms of mucus penetration and stimulus-responsive drug release. This design not only enhances the deposition of the drug in the lungs but also achieves efficient treatment of ALI by precisely controlling drug release, demonstrating its potential as an advanced strategy for treating respiratory diseases.
研究领域:
药学
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纳米技术
·
呼吸医学
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生物医学工程
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2020
·Vol. 48
·期 9
·830-839
·
IF 3.231
Tingying Jiao,Xinpeng Yao,Yingyuan Zhao,Yanying Zhou,Yue Gao,Shicheng Fan,Panpan Chen,Xuan Li,Yiming Jiang,Xiao Yang,Frank J. Gonzalez,Min Huang,Huichang Bi
Dexamethasone (Dex), a widely prescribed anti-inflammatory drug, was reported to induce liver enlargement (hepatomegaly) in clinical practice and in animal models. However, the underlying mechanisms are not elucidated. Dex is a known activator of pregnane X receptor (PXR). Yes-associated protein (YAP) has been implicated in chemically induced liver enlargement. Here, the roles of PXR and YAP pathways were investigated in Dex-induced hepatomegaly. Upregulation of PXR downstream proteins, including cytochrome P450 (CYP) 3A11, 2B10, and organic anion transporter polypeptide 2 (OATP2) (also known as SLCO1A4 and SLC21A5 in mouse), indicated PXR signaling was activated after high dose of Dex (50 mg/kg, i.p.), and Dex at 100 μM activated PXR in the dual-luciferase reporter gene assay. Dex also increased the expression of total YAP, nuclear YAP, and YAP downstream proteins, including connective tissue growth factor and cysteine-rich angiogenic inducer 61, indicating activation of the YAP pathway. Furthermore, nuclear translocation of YAP was promoted by activation of PXR. However, hepatocyte proliferation was inhibited with significant decrease in the expression of proliferation-related proteins cyclin D1 and proliferating cell nuclear antigen as well as other regulatory factors, such as forkhead box protein M1, c-MYC, and epidermal growth factor receptor. The inhibitory effect of Dex on hepatocyte proliferation was likely due to its anti-inflammation effect of suppression of inflammation factors. β-catenin staining revealed enlarged hepatocytes, which were mostly attributable to the accumulation of lipids, such as triglycerides. In summary, high-dose Dex increased liver size accompanied by enlarged hepatocytes, and this was due to the activation of PXR/YAP and their effects on lipid accumulation but not hepatocyte proliferation. These findings provide new insights for understanding the mechanism of Dex-induced hepatomegaly.
研究领域:
药理学
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肝病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yongguo Xiang,Zhu Qiu,Yuanfu Ding,Miaomiao Du,Ning Gao,Huijie Cao,Hangjia Zuo,Hong Cheng,Xiang Gao,Shijie Zheng,Wenjuan Wan,Xiaobei Huang,Ke Hu
Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.
研究领域:
药学
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眼科学
·
纳米技术
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药物递送系统
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炎症
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氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Hailin Liu,Lian Zhou,Xifeng Wang,Qingcui Zheng,Fenfang Zhan,Lanqian Zhou,Yao Dong,Yanhong Xiong,Pengcheng Yi,Guohai Xu,Fuzhou Hua
The side effects of high-dose dexamethasone in anti-infection include increased ROS production and immune cell apoptosis. Dexamethasone effectively activates serum/glucocorticoid-regulated kinase 1 (SGK1), which upregulates various ion channels by activating store-operated calcium entry (SOCE), leading to Ca 2+ oscillations. PIEZO1 plays a crucial role in macrophages' immune activity and function, but whether dexamethasone can regulate PIEZO1 by enhancing SOCE via SGK1 activation remains unclear. The effects of dexamethasone were assessed in a mouse model of sepsis, and primary BMDMs and the RAW264.7 were treated with overexpression plasmids, siRNAs, or specific activators or inhibitors to examine the relationships between SGK1, SOCE, and PIEZO1. The functional and phenotypic changes of mouse and macrophage models were detected. The results indicate that high-dose dexamethasone upregulated SGK1 by activating the macrophage glucocorticoid receptor, which enhanced SOCE and subsequently activated PIEZO1. Activation of PIEZO1 resulted in Ca 2+ influx and cytoskeletal remodelling. The increase in intracellular Ca 2+ mediated by PIEZO1 further increased the activation of SGK1 and ORAI1/STIM1, leading to intracellular Ca 2+ peaks. In the context of inflammation, activation of PIEZO1 suppressed the activation of TLR4/NFκB p65 in macrophages. In RAW264.7 cells, PIEZO1 continuous activation inhibited the change in mitochondrial membrane potential, accelerated ROS accumulation, and induced autophagic damage and cell apoptosis in the late stage. CaMK2α was identified as a downstream mediator of TLR4 and PIEZO1, facilitating high-dose dexamethasone-induced macrophage immunosuppression and apoptosis. PIEZO1 is a new glucocorticoid target to regulate macrophage function and activity. This study provides a theoretical basis for the rational use of dexamethasone.
研究领域:
免疫学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2018
·Vol. 16
·期 2
·643-648
·
IF 1.41
Sibo Li,Haitao Jiang,Xiaohua Gu
Glucocorticoids (GCs) are widely used to treat chronic diseases. Prolonged and/or overdose administration of GCs has many side‑effects to human health including GC‑induced osteoporosis (GIOP). In this investigation, the objective was to assess the influence that echinacoside (ECH) exerts upon dexamethasone‑treated murine osteoblastic MC3T3‑E1 cells. We found that ECH (5, 10, 20 and 40 mg/l) inhibited dexamethasone (1,000 nM)‑suppressed cell viability as demonstrated by Cell Counting Kit‑8 (CCK‑8) assay. The dose of 10 mg/l was selected for the following experiments because this dose had a better effect than the dose of 5 mg/l, and the doses >10 mg/l had a similar effect as this dose. ECH (10 mg/l) or pifithrin‑α (PFT‑α) (a p53 inhibitor, 20 µM) suppressed dexamethasone‑induced MC3T3‑E1 apoptosis as illustrated by Annexin V/propidium iodide (PI) double‑labeling flow cytometry analysis. ECH or PFT‑α treatment also alleviated dexamethasone's action of inhibiting Bcl‑2 expression as well as dexamethasone's action of stimulating on the expression of p53 and Bax. Moreover, lentivirus mediated‑p53 overexpression reversed the effects of ECH in dexamethasone‑treated MC3T3‑E1 cells, suggesting that ECH induced anti‑apoptotic effects in dexamethasone‑treated osteoblasts via p53‑dependent pathway. In summary, ECH has a protective effect against osteoblastic cell apoptosis induced by dexamethasone, suggesting that ECH may have potentials for clinical application in the treatment of GIOP.
研究领域:
药理学
·
细胞生物学
·
骨骼健康
✓ 已验证
DOI
PubMed
高影响因子
ACS Pharmacology & Translational Science
·
2026
·
IF 4
Xianlan Chen,Lu Zhang,Yan Zheng,Haiyang Chi,Rongrong Zhao,Kang Hu,Jiashan Zhu,Mi Liu
Knee osteoarthritis (KOA) has no effective nonsurgical treatment. Intra-articular therapy constitutes an effective localized intervention; however, persistent lymphatic drainage and synovial vascular exchange lead to rapid drug elimination. Encapsulating bioactive agents into microsphere delivery platforms enables localized intra-articular administration, with their scaffold-based spherical architecture serving as pharmaceutical and cellular carriers or tissue engineering scaffolds, representing a highly promising therapeutic avenue for KOA. Herein, PLGA was employed to prepare microspheres and a sustained-release microsphere formulation (MPs PLGA DSP@COLI) was prepared for KOA therapeutics, co-encapsulating type I collagen (COLI) and dexamethasone sodium phosphate (DSP). Characterization revealed uniform particle size distribution, favorable dispersibility, and extended-release kinetics. Functional assessments demonstrated robust anti-inflammatory efficacy and enhanced chondrocyte-mediated extracellular matrix deposition. Histopathological and immunohistochemical analyses demonstrated preserved cartilage matrix integrity, augmented COLII synthesis, diminished inflammatory cellular infiltration, and maintained homeostasis of cartilage matrix components, concomitant with reduced OARSI and synovitis scores. These effects collectively suppressed synovial hyperplasia and inflammation and suggested potential improvement in joint conditions. Overall, MPs PLGA DSP@COLI combines the pharmacological anti-inflammatory properties of DSP with the extracellular matrix-related biological functions of COLI, establishing an innovative "drug-device combination" therapeutic paradigm, which represents a promising therapeutic strategy for KOA.
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2021
·
IF 5.268
Mingyue Ai,Chuanjia Guo,Liwei Wang,Ming Hu,Kaixu Xu,Chen Li,Zhimin Zhou
It is important to achieve precise surface charge manipulation of non-spherical drug microcrystals using facile and time-efficient methods for local drug delivery. In this study, silk-coated dexamethasone (DEX) non-spherical microcrystals were synthesized by precipitation technique followed by alternate deposition of poly(allylamine hydrochloride) (PAH) (or PAH-coated Fe 3 O 4 ) and silk fibroin (SF) via layer-by-layer assembly. EDC and glutaraldehyde were employed to manipulate positive or negative charge of particles by simple chemical cross-linking reactions, respectively. In vivo assessment was carried out by intratympanic (IT) injection of DEX non-spherical microcrystals in guinea pigs. In vivo pharmacokinetic results demonstrate that negatively charged DEX microcrystals appeared to improve outcomes of inner ear delivery in comparison to positively-charged counterparts. This is partly because of the adhesive features of the SF. The present study may provide new ideas to construct surface charge-tunable drug delivery vehicles that are capable of crossing biological barriers, especially for inner ear delivery due to the simple and practical strategy.
研究领域:
药学
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Zhidong Sun,Fan Wu,Huichang Gao,Kai Cui,Mengyue Xian,Jianglong Zhong,Ye Tian,Song Fan,Gang Wu
Additive manufacture (AM) has been widely and rapidly applied in fabrication of 3D porous scaffolds for tissue engineering applications. For synthetic polymers of high melting temperature, the melting-extruding technique is the most applied AM method for such fabrication of polymer porous scaffolds. This results in a big challenge to directly process the scaffolds using the polymers and thermosensitive substances simultaneously because of deactivation under high temperature. In this article, the selective laser sintering (SLS) method was proposed to make a poly(l-lactic acid) (PLLA) porous scaffold containing dexamethasone (Dex) simultaneously. Dex was encapsulated in two groups of PLLA–bioactive glass (BG) composite microspheres with an average diameter of 115–120 μm and loading amounts of 0.68 ± 0.09 and 0.84 ± 0.10 μg/mg, respectively. The drug-loading composite microspheres were then fabricated into scaffolds under a laser fluence of 0.83–2.08 J/mm2. The average pore size and compressive modulus for the porous scaffold were 450–500 μm and 18–25 MPa, respectively. Drug release experiments showed that Dex was released from the scaffold in a controlled manner until about a month. The eluting time of HPLC tests before or after SLS processing both presented at 4 min indicated no chemical structure changes for the drug. Ex vivo cell experiments also testified the comparable effect of released Dex with commercial products, showing that the bioactivities were not affected after SLS. Implantation of the composite scaffolds in rat cranium defects demonstrated that new bone and blood vessel formation was faster in the Dex-releasing scaffolds than in the groups without drug loading.
研究领域:
材料科学
·
生物医学工程
·
组织工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
Applied Physiology Nutrition and Metabolism
·
2018
·Vol. 44
·期 1
·
IF 2.518
Yu Qiao,Guoqiang Fan,Jun Guo,Shixing Gao,Ruqian Zhao,Xiaojing Yang
Zinc-α2-glycoprotein (ZAG) has been demonstrated to play a role in stimulating lipid mobilization under normal conditions. However, further studies are required to determine whether ZAG overexpression can alleviate the reduction in plasma lipid levels under stress conditions. In the present study, we investigated the effects of ZAG on lipometabolism in white adipose tissue (WAT) after dexamethasone (DEX) stimulation using C57BL/6 male mice as the experimental models. Transcript and protein levels of genes associated with the β-adrenoreceptor (β-AR)/cyclic adenosine monophosphate/protein kinase a (PKA) pathway, lipid mobilization, and energy metabolism were determined by quantitative real-time polymerase chain reaction and Western blotting. Plasma levels of nonesterified fatty acid (NEFA) were measured using an automatic biochemical analyzer. Results indicated that plasma NEFA levels were decreased in the DEX group, but NEFA levels were rescued by ZAG overexpression. ZAG overexpression resulted in the upregulation of β3-AR and phosphorylated PKA protein relative to those of the DEX group. Analysis of lipometabolism showed that protein levels of phosphorylated hormone-sensitive lipase was reduced upon DEX treatment but were restored by ZAG overexpression. For energy metabolism, ZAG significantly upregulated the protein expression of carnitine palmitoyltransferase1a and cytochrome c oxidase subunit 1 relative to those of the DEX group. In conclusion, ZAG could alleviate DEX-induced decrease in plasma NEFA levels and this could be associated with the promoting lipid mobilization in WAT.
研究领域:
药理学
·
内分泌学
·
代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）