MATERIALS LETTERS
·
2012
·
IF 2.307
Chang Gao,Yurong Cai,Xiangdong Kong,Guoxiang Han,Juming Yao
The injectable chitosan/β-glycerophosphate (CS/GP) hydrogels were prepared with dexamethasone (Dex)/recombinant human bone morphogenetic protein (rhBMP-2) loaded hydroxyapatite nanoparticles (nHAP). The obtained samples were characterized by TEM, SEM, XRD and nitrogen adsorption tests, and the effect of Dex and rhBMP-2 on the mesenchymal stem cells (MSCs) was evaluated. The results showed that nHAP could be dispersed homogeneously in the matrix of injectable CS/GP hydrogels and the combination of Dex and rhBMP-2 could promote the proliferation and osteoblastic differentiation of MSCs, indicating that the prepared injectable CS/GP hydrogels with Dex and rhBMP-2 loaded nHAP have great potential in different orthopedic regenerative applications.
研究领域:
生物材料学
·
再生医学
·
骨科
✓ 已验证
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Wali Muhammad,Jiaqi Zhu,Zihe Zhai,Jieqi Xie,Jiahang Zhou,Xudong Feng,Bing Feng,Qiaoling Pan,Shifen Li,Rajiu Venkatesan,Pan Li,Hongcui Cao,Changyou Gao
The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients as currently seen in coronavirus disease 2019 (COVID-19). There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to lung to reduce the burden of high doses of medications and attenuate inflammatory cells and pathways. Herein, we prepared dexamethasone-loaded ROS-responsive polymer nanoparticles ( [email protected] NPs) by a modified emulsion approach, which achieved high loading content of DEX (11.61 %). DEX was released faster from the [email protected] NPs in a ROS environment, which could scavenge excessive ROS efficiently both in vitro and in vivo . The PFTU NPs and [email protected] NPs showed no hemolysis and cytotoxicity. Free DEX, PFTU NPs and [email protected] NPs shifted M1 macrophages to M2 macrophages in RAW264.7 cells, and showed anti-inflammatory modulation to A549 cells in vitro . The [email protected] NPs treatment significantly reduced the increased total protein concentration in BALF of ALI mice. The delivery of [email protected] NPs decreased the proportion of neutrophils significantly, mitigated the cell apoptosis remarkably compared to the other groups, reduced M1 macrophages and increased M2 macrophages in vivo . Moreover, the [email protected] NPs had the strongest ability to suppress the expression of NLRP3, Caspase1, and IL-1β. Therefore, the [email protected] NPs could efficiently suppress inflammatory cells, ROS signaling pathways, and cell apoptosis to ameliorate LPS-induced ALI. Statement of Significance The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients. There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to modulate the inflammatory disorder and suppress the expression of ROS and inflammatory cytokines. The inhaled [email protected] NPs prepared through a modified nanoemulsification method suppressed the activation of NLRP3, induced the polarization of macrophage phenotype from M1 to M2, and thereby reduced the neutrophil infiltration, inhibited the release of proteins and inflammatory mediators, and thus decreased the acute lung injury in vivo .
研究领域:
药学
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纳米技术
·
肺科学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
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IF 10.273
Sheng Ma,Wantong Song,Yudi Xu,Xinghui Si,Dawei Zhang,Shixian Lv,Chenguang Yang,Lili Ma,Zhaohui Tang,Xuesi Chen
Tumor is known as “a wound that does not heal”. Tumor-promoting inflammation plays a crucial role in carcinogenesis, tumor progression, tumor metastasis, as well as chemotherapy resistance. Therefore, reducing tumor-promoting inflammation may be a key aspect in targeting the tumor microenvironment for cancer therapy. Dexamethasone (DEX), a commercial drug in the treatment of many different inflammatory diseases, can effectively inhibit the release of substances causing inflammation. However, as a corticosteroid medication, direct use of DEX results in many severe side effects. In this study, a redox and pH dual sensitive polypeptide-DEX conjugate (L–SS–DEX) was synthesized, and the L–SS–DEX dramatically increased the tumoral accumulation of DEX in murine colorectal cancer model (CT26) compared to free DEX. Importantly, at equal dose (10 mg/kg), L–SS–DEX showed superior antitumor activity over free DEX: 86% tumor suppression rate of L–SS–DEX treatment group compared to 49% of free DEX treatment group. Further analysis of the tumor tissues showed that cyclooxygenase-2 (COX-2) and α-smooth muscle actin (α-SMA) were significantly reduced after the L–SS–DEX treatment compared with control groups. In addition, the immunosuppressive microenvironment of the CT26 tumor was effectively relieved after L–SS–DEX treatment, characterized by increased CD8 + T cell infiltration , increased ratio of M1 over M2 macrophages, as well as markedly decrease in regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The above results suggest that anti-inflammatory drugs hold great potential in modulating the tumor microenvironment when delivered properly, and can also result in significant tumor inhibition effects. Since dramatic amounts of anti-inflammatory drugs have been used in clinic, our results may provide improved tumor therapy options of using anti-inflammatory drugs for cancer therapy.
研究领域:
肿瘤学
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药学
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免疫学
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 4
·2385-2392
·
IF 1.448
Li Li,Qiuhong Li,Lei Wei,Zhongfu Wang,Wei Ma,Fangying Liu,Yanhua Shen,Shanfang Zhang,Xiulian Zhang,Huiping Li,Yechang Qian
Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)‑induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α‑smooth muscle actin (α‑SMA), MMP2/9 and phosphorylated‑Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α‑SMA and p‑Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.
研究领域:
药理学
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呼吸医学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Muqing Xu,Dong Ma,Dongxiu Chen,Jieqing Cai,Qiaofang He,Fan Shu,Jie Tang,Hongzheng Zhang
Cochlear inflammatory response after cochlear implantation (CI) is an important mechanism for implantation trauma and hearing loss. The hearing loss was also caused by damage to auditory hair cells (HCs), whereas ion homeostasis within the cochlea can ensure survival of HCs. In our study, pure hyaluronic acid (HA) was crosslinked with 1, 4-butanediol diglycidyl ether (BDDE) and the successful preparation of the cross-linked hydrogel (CHA) was confirmed by rheological characteristics and FTIR spectra. Artificial perilymph (APL) was prepared to simulate the ion homeostasis microenvironment within scala tympani of human cochlear, and served as the major component of artificial perilymph soaked CHA (APL-CHA). The conductivity experiment indicated that APL-CHA is more suitable to the requirements of the electrical conductivity in scala tympani. The electrode coating process found that the extrusion coating method have advantages of controllable adhesive capacity of APL-CHA, uniform coating thickness and smooth surface as compared to common method. Due to CI surgery application requirement, optimization of coating process was selected as follows: extrusion coating method, degree of 3.6 vol%, pinhole diameter of 32G (110 μm), pressure of 200 ± 15.81 Psi. Controlled dexamethasone 21-phosphate sodium salt (DSP) release of 20 days could be demonstrated using the hydrogel filled reservoir via a validated HPLC method. The morphological structure of CHA showed different sizes of porous structure among APL-CHA provided structural basis for drug delivery. L929 fibroblasts culture and Spiral Ganglion Neuron Explants culture results revealed that APL-CHA possesses fine biological compatibility. APL-CHA shows a promising application in CI surgery and has great potential in preventing hearing loss with well simulation of ion homeostasis within the cochlear, local DSP delivery for target anti-inflammatory, approximate conductivity within the scala tympani and optimization of electrode coating process.
研究领域:
生物医学工程
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药剂学
·
听力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Guoxin Tan,Shihui Yu,Jinyu Li,Weisan Pan
This study aims to explore a novel composite thermosensitive in situ gelling formulation which the nanostructured lipid carriers (NLC) was incorporated into hydroxypropyltrimethyl ammonium chloride chitosan (HACC)-based hydrogels, and the resulting formulation investigated for its potential to act as a potential sustained ocular delivery system. NLC formulation loaded with dexamethasone (DXM) were prepared using the melt-emulsification method. The particle size, zeta potential , encapsulation efficiency, and morphological properties of the NLC were characterized. The HACC was synthesized and structure was analyzed by FT-IR and 1 H NMR . A thermosensitive hydrogel was designed and prepared by simply mixing HACC and β-glycerophosphate (β-GP). The obtained formulation showed a rapid solution-to-gel transition at 35 °C. The NLC were then incorporated in HACC/β-GP hydrogel to form a NLC-loaded hydrogel carrier. In vitro release studies, 88.65% of total DXM was released from the NLC-HACC/GP gel within 3 days, indicating DXM-based NLC-gel could release drug sustainably. Taken together, DXM-based NLC-HACC/GP gel is a promising drug delivery system.
研究领域:
药剂学
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生物材料
·
眼科药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Chen Dongxiu,Luo Yanjing,Pan Jing,Chen Anning,Ma Dong,Xu Muqing,Tang Jie,Zhang Hongzheng
Cochlear implantation (CI) is the major treatment for severe sensorineural hearing loss. However, the fibrotic tissue forming around the electrodes reduces the treatment effectiveness of CI. Dexamethasone (DEX) is usually applied routinely in perioperative treatment of cochlear implantation (CI), but its diffusion in the inner ear after systemic administration is limited. In the present study, an electrode coated with polycaprolactone (PCL) loaded with dexamethasone was developed with a simple preparation process to maintain the stability of the electrode itself. The DEX-loaded PCL coating has good biocompatibility and does not change the smoothness, flexibility, or compliance of the implant electrode. Stable and effective DEX concentrations were maintained for more than 9 months. Compared with the pristine electrode, decreasing intracochlear fibrosis, protection of hair cells and spiral ganglion cells, and better residual hearing were observed 5 weeks after PCL-DEX electrode implantation. The PCL-DEX electrode has great potential in preventing hearing loss and fibrosis by regulating macrophages and inhibiting the expression of the fibrosis-related factors IL-1β, TNF-α, IL-4, and TGF-β1. In conclusion, the PCL-DEX electrode coating shows promising application in CI surgery.
研究领域:
耳鼻喉科
·
生物材料
·
神经科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Wenyu Miao,Lingling He,Yong Zhang,Xiaoyu Zhu,Yangming Jiang,Pengpeng Liu,Tao Zhang,Chunqi Li
Glucocorticoids (GCs) have been widely detected in the aquatic system. However, the hazardous effects of GCs on aquatic organisms were underestimated, and the mechanisms of GCs-induced toxic effects in fish were largely unknown. The zebrafish larvae at 3 dpf were exposed to dexamethasone (DEX) for 48 h, and the toxic effects and the underlying mechanisms were investigated in the current study. The T cells were ablated in zebrafish larvae after being treated with 1, 3, 10, 30 and 100 μM of DEX for 48 h. In addition, osteoporosis was induced and the regeneration of the caudal fin was inhibited, by 48 h-exposure to 10, 30 and 100 μM of DEX. The transcriptomic analysis, biochemical parameters and gene expression profiles revealed that ferroptosis possibly contributed to the DEX-induced toxic effects in zebrafish larvae. Finally, Fer-1 treatment partially attenuated the DEX-induced T cell ablation, but not osteoporosis in zebrafish larvae. Taken together, the current study proved the toxic effects of DEX on zebrafish larvae, and elucidated that ferroptosis was involved in DEX-induced toxicity, providing strong evidence for the toxic effects of GCs on aquatic organisms.
研究领域:
水生毒理学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Neuroscience
·
2022
·
IF 5.152
Song Yiming,Liu Xuanhui,Yuan Jiangyuan,Sha Zhuang,Jiang Weiwei,Liu Mingqi,Qian Yu,Gao Chuang,Gong Zhitao,Luo Hongliang,Zhou Xin,Huang Jinhao,Jiang Rongcai,Quan Wei
Intracerebral hemorrhage (ICH) is a fatal disease with high mortality and poor prognosis that triggers multiple severe brain injuries associated with an inflammatory cascade response that cannot be treated with any effective medication. Atorvastatin (ATO) suppresses inflammation, alleviates brain trauma, and eliminates subdural hematoma. Dexamethasone (DXM) also has the capacity to inhibit inflammation. Thus, we combined ATO with low-dose DXM to treat ICH mice in vivo to examine whether the combined treatment can inhibit secondary inflammation around the cerebral hemorrhage and decrease overall mortality. Compared to the monotherapy by either ATO or DXM, the combined treatment significantly improves the survivorship of the ICH mice, accelerates their recovery of impaired neurological function, and modulates the circulating cytokines, oxidative products, and apoptosis. Moreover, the benefit of ATO-DXM combination therapy was most pronounced on day 3 after dosing compared to ATO or DXM alone. Thus, early administration of ATO combined with low-dose-DXM promotes better survival of ICH and improves neurological function by reducing neuroinflammation and brain edema in their early phase.
研究领域:
神经科学
·
药理学
·
炎症
·
神经病学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Ning Li,Lianyan Xie,Yicheng Wu,Yan Wu,Yongjia Liu,Yiming Gao,Jie Yang,Xiuyin Zhang,Liting Jiang
Periodontitis is a bacterial-induced, chronic inflammatory disease characterized by progressive destruction of tooth-supporting structures. Pathogenic bacteria residing in deep periodontal pockets after traditional manual debridement can still lead to local inflammatory microenvironment, which remains a challenging problem and an urgent need for better therapeutic strategies. Here, we integrated the advantages of metal-organic frameworks (MOFs) and hydrogels to prepare an injectable nanocomposite hydrogel by incorporating dexamethasone-loaded zeolitic imidazolate frameworks-8 (DZIF) nanoparticles into the photocrosslinking matrix of methacrylic polyphosphoester (PPEMA) and methacrylic gelatin (GelMA). The injectable hydrogel could be easily injected into deep periodontal pockets, achieving high local concentrations without leading to antibiotic resistance. The nanocomposite hydrogel had high antibacterial activity and constructs with stable microenvironments maintain cell viability, proliferation, spreading, as well as osteogenesis, and down-regulated inflammatory genes expression in vitro . When evaluated on an experimental periodontitis rat model, micro-computed tomography and histological analyses showed that the nanocomposite hydrogel effectively reduced periodontal inflammation and attenuated inflammation-induced bone loss in a rat model of periodontitis. These findings suggest that the nanocomposite hydrogel might be a promising therapeutic candidate for treating periodontal disease.
研究领域:
牙科材料
·
药学
·
纳米技术
·
炎症
·
生物材料
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2026
·
IF 12.6
Chenxiao Chu,Xi Chen,Yaxin Deng,Jie Zhang,Xiaoshuang Bi,Yunfeng Ma,Mingli Wei,Jiansong Zhao,Haibing He,Jingxin Gou,Tian Yin,Xing Tang,Li Yang,Yu Zhang
Corneal neovascularization (CNV), an inflammation-driven pathological process responsible for irreversible vision loss, remains an urgent unmet challenge in ophthalmic medicine. Current interventions—ranging from surgery to topical steroids—fail to prevent recurrence or evade severe side effects like intraocular hypertension and even corneal ulceration. Here, we introduce CL-Peptide-Dex, a transformative contact lens (CL) engineered for matrix metalloproteinase-9 (MMP-9)-responsive dexamethasone (Dex) release, to resolve this decades-long challenge. By grafting dexamethasone on the lens surface via an MMP-9-cleavable peptide linker (GPLGLAGC), CL-Peptide-Dex achieves disease-adaptive drug delivery: rapid release during acute inflammation and sustained release throughout CNV progression. Unlike conventional drug-eluting systems, this surface-grafting strategy eliminates burst release while preserving lens transparency and oxygen permeability. In the rabbit corneal neovascularization model, a single administration of CL-Peptide-Dex could maintain a stable Dex level for 7 days, suppressed VEGF by 77.5%, and reduced neovascular area by 79.5%. Critically, CL-Peptide-Dex avoided intraocular pressure spikes and exhibited good corneal biocompatibility and compliance, enabling safe extended wear. By integrating MMP-9-responsive precision delivery with patient-friendly design, CL-Peptide-Dex represents a significant advance in precision ophthalmology.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Xiaochen Ma,Yubo Cui,Min Zhang,Qinghua Lyu,Jun Zhao
Introduction Oxidant stress, abnormal angiogenesis, and inflammation are three key factors contributing to the development of ocular neovascular diseases (ONDs). This study aims to develop a multifunctional nanodrug, DEX@MPDA-Arg@Si (DMAS), which integrates mesoporous polydopamine, vascular endothelial growth factor (VEGF)-siRNA, and dexamethasone (DEX) to address these therapeutic targets.Methods Physicochemical properties of DMAS were measured using transmission electron microscopy and a nanoparticle size analyzer. The encapsulation efficiency and drug loading capacity of DMAS were measured using a UV-visible spectrophotometer. The in vivo therapeutic efficacy and ocular safety of DMAS were evaluated using three established mouse models, including the alkali burn-induced corneal neovascularization (CoNV) model, the oxygen-induced retinopathy (OIR) model, and the laser-induced choroidal neovascularization (CNV) model.Results The DMAS nanoparticles demonstrated a uniform bowl-like shape with an average size of 264.9 ± 2.5 nm and a zeta potential of −28.2 ± 4.2 mV. They exhibited high drug-loading efficiency (36.04 ± 3.60% for DEX) and excellent biocompatibility. In vitro studies confirmed its potent antioxidant, anti-inflammatory, and anti-apoptotic properties. In vivo, DMAS treatment led to significant therapeutic effects across all models. It effectively inhibited CoNV, promoted corneal repair, and modulated inflammation in the alkali burn model. In the OIR model, DMAS reduced retinal neovascularization by decreasing VEGF expression. In the laser-induced CNV model, it significantly reduced the CNV area and lesion thickness.Conclusion This research developed a multifunctional nanodrug, DMAS, capable of co-delivering VEGF-siRNA and DEX, offering synergistic therapeutic benefits for treating ONDs. The DMAS nanodrug demonstrates promising anti-inflammatory, antioxidative, and anti-angiogenic effects, highlighting its potential as a versatile and effective treatment for multiple ocular conditions.
研究领域:
药学
·
纳米技术
·
眼科
·
分子生物学
✓ 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）