DRUG DELIVERY
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2016
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IF 4.843
Aiguo Zeng,Kai Dong,Maoling Wang,Jinyao Sun,Yalin Dong,Ke Wang,Chenning Guo,Yan Yan,Lu Zhang,Xianpeng Shi,Jianfeng Xing
Context: Dexamethasone is the major drug in the treatment of ulcerative colitis (UC). However, the extensive or long-time use of dexamethasone causes many toxic side-effects. Ion exchange resins react with external-ions through their own functional groups and Eudragit S occurs degradation when pH > 7. These features make them suitable for oral delivery system.Objective: Resin microcapsule (DRM) composed by 717 anion exchange resin and Eudragit S100 was used to target dexamethasone to the colon to improve its treatment effect on UC and reduce its toxic side-effects.Results: Dexamethasone sodium phosphate (DXSP) was sequentially encapsulated in 717 anion-exchange resin and Eudragit S100 to prepare the DXSP-loaded resin microcapsule (DXSP-DRM). The in vitro release study and in vivo study of pharmacokinetics and the intestinal drug residues in rat demonstrated the good colon-targeting of DXSP-DRM. Moreover, the DXSP-DRM can reduce the toxic side-effects induced by DXSP and have good therapeutic effects on colitis mouse induced by 2,4,6-trinitrobenzenesulfonic acid.Discussion: Dexamethasone can be targeted to the colon by DRM, thereby enhancing its treatment effect and reducing its toxic side effects.Conclusion: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeted preparations.
研究领域:
药理学
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药物递送系统
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炎症性肠病
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DOI
PubMed
高影响因子
BIOMACROMOLECULES
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2017
·
IF 5.246
Jiabing Ran,Hao Zeng,Janak Lal Pathak,Pei Jiang,Yi Bai,Pan Yan,Guanglin Sun,Xinyu Shen,Hua Tong,Bin Shi
In bone tissue engineering (BTE), most of the currently developed scaffolds still lack the ability to demonstrate high porosity and high mechanical strength simultaneously or the ability to maintain bioactivity and sustained release of loaded biofactors. In this work, we constructed an anisotropic triple-pass tubular framework within a lyophilized porous GEL scaffold using FP, which was prepared by coating DEX-covered Whatman paper (WP) using the silk fibroin (SF) membrane with β-sheet conformation. This novel structural design endowed the functionalized paper frame (FPF)/scaffold implant high porosity, high mechanical strength, and sustained DEX delivery capability. Specifically, its porosity was as high as 88.2%, approximating that of human cancellous bone. The pore diameters of the implant ranged from 50 to 350 μm with an average pore diameter of 127.7 μm, indicating proper pore sizes for successful diffusion of essential nutrients/oxygen and bone tissue-ingrowth. Owing to the construction of double-network-like structure, the FPF/scaffold implant demonstrated excellent mechanical properties both in dry (174.7 MPa in elastic modulus and 14.9 MPa in compressive modulus) and wet states (59.0 MPa in elastic modulus and 3.3 MPa in compressive modulus), indicating its feasibility for in vivo implantation. Besides, the FPF/scaffold implant exhibited long-term DEX releasing behavior (over 50 days) with constant release rate in phosphate buffered saline (PBS). Murine osteoblasts MC3T3-E1 cultured in the porous FPF/scaffold implant had excellent viability. Furthermore, the cells cocultured with the FPF/scaffold implant showed positive proliferation, osteogenic differentiation, and calcium deposition. Twenty-eight days after implantation, extensive osteogenesis was observed in the rats treated with the FPF/scaffold implants. The anisotropic triple-pass tubular framework of the FPF/scaffold implant demonstrates structural similarities to the long bone. Therefore, this novel FPF/scaffold implant could be a better alternative for long bone defect repair.
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PubMed
高影响因子
ARCHIV DER PHARMAZIE
·
2025
·Vol. 358
·期 11
·e70121
·
IF 3.6
Ling Jiang,Jiangming Zhong,Huixiong Chen,Yi Li,Qi Zhou,Miaohong Yang,Li Lin,Peng Shu,Zhiyun Du
Retinoic acid receptor-related orphan receptor gamma-t (RORγt) is one of the nuclear receptor transcription factors that plays a key role in the differentiation of pro-inflammatory IL-17 + T helper cells. Recently, RORγt has attracted increasing attention as a potential drug target for the treatment of several human inflammatory diseases, including psoriasis and Crohn's disease. In this study, we revealed that ergosterol (ERG) was a novel RORγt inverse agonist, which decreased RORγt transcriptional activity, to regulate collagen fiber deposition and to inhibit pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-17, IL-22, and IL-23 in the skin lesions of IMQ-induced mice with psoriasis. Furthermore, ERG could repair the epidermal barrier function by upregulating tight junction proteins, such as claudin, occludin, and ZO-1, thereby alleviating psoriasis symptoms. These findings suggested that ERG might be used as a promising novel RORγt inverse agonist in the management of psoriasis.
研究领域:
免疫学
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皮肤病学
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分子药理学
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炎症性疾病
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DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
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IF 5.4
Jiangtao Guo,Junjie Liu,Mingwei Wang,Yuhua Zhang,Ziyu Zhang,Martien Cohen Stuart,Junchao Chen,Weiping Tang,Xuhong Guo,Dahu Qi,Tao Liu
Spinal cord injury (SCI) is a serious neurological disease accompanied by neuroinflammatory responses. Recently, nanosized drug delivery systems have attracted attention for SCI treatment by improving solubility and bioavailability and providing sustained drug release. Protein-based nanoparticles can be biocompatible but often require chemical cross-linkers for structural stability, raising biosafety concerns. Here, we introduce a β-sheet-driven physical cross-linking approach to fabricate nanoparticles without chemical cross-linkers, namely by employing gelatin (Gel) and silk fibroin (SF) as proteins. This coassembly approach ensures structural integrity, enables enzyme-responsive degradation, and allows precise size control with narrow size distributions. Gel/SF particles can load dexamethasone (DEX) with a high drug loading (∼72%), exhibiting long-term stability and enzyme-triggered release. In vitro, these nanoparticles suppress pro-inflammatory cytokines and promote M2 phenotype microglial polarization, suggesting their neuroinflammation-regulating potential. Gel/SF particles may be a biocompatible, cross-linker-free protein-based drug delivery system, offering a promising platform for SCI treatment and broader applications in neuroinflammatory disorders.
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高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yongbin Wang,Han Zhang,Zhili Xu,Weihang Zhu,Sheng Chang,Jiahao Wei,Shuqing Chen,Yong Liu,Weiqing Kong,Jianwei Guo
Large bone defects present significant clinical challenges due to limitations of current treatments including immune rejection, infection, and poor osteoinductive capacity. This study developed a novel biomimetic piezoelectric scaffold system combining 3D-printed potassium sodium niobate/nano-hydroxyapatite/polylactic acid (KNN/nHA/PLA) scaffolds with icariin-loaded gelatin methacryloyl hydrogel (ICA@G/NHP) to synergistically promote bone regeneration and immunomodulation. The composite scaffolds demonstrated excellent mechanical properties and stable piezoelectric output under ultrasonic activation. In vitro studies revealed that ultrasonic stimulation was essential for activating piezoelectric effects, significantly enhancing osteogenic differentiation of bone marrow mesenchymal stem cells through upregulation of ALP, RUNX2, and COL1 expression. The incorporated icariin effectively promoted endothelial cell migration and induced M2 macrophage polarization via C-type lectin receptor signaling pathway, creating a pro-regenerative immune microenvironment. In vivo validation using rat cranial and rabbit femoral condyle defect models demonstrated superior bone regeneration with enhanced bone mineral density, bone volume fraction, and mature trabecular architecture compared to controls. Immunofluorescence analysis confirmed sustained M2 macrophage dominance and suppressed inflammatory responses. RNA sequencing identified PI3K/Akt as the central mechanotransduction pathway mediating scaffold effects. This integrated platform addresses dual challenges of osteogenesis and immune regulation, offering a promising therapeutic strategy for critical-sized bone defect repair through ultrasound-activated piezoelectric stimulation combined with targeted immunomodulation.
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Chengwei Wu,Zhiyuan Zhou,Weiming Lin,Jiamin Zhang,Kaicheng Xu,Xin Xin,Xuzhao He,Wenjian Weng,Gaorong Han,Chengyun Ning,Zuobing Chen,Kui Cheng
Time-dependent modulation of macrophage polarization and effective promotion of osteogenesis are essential for enhancing bone regeneration. This study designed composite films based on graphene nanosheets (Gr) and poly(vinylidene fluoride-trifluoroethylene) (PVTF), which can simultaneously provide surface potential and photothermal stimulation. The 0.3 wt.% Gr content not only delivered photothermal properties, but also improved the crystalline and piezoelectric properties of PVTF. The electrically polarized composite film with the d33 of −22 pC N −1 achieved the optimal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under appropriate illumination parameters. Meanwhile, the surface potential of the composite film can promote both M1 and M2 polarization of macrophages, which can be transformed to significant M2 polarization after photothermal stimulation, showing the potential for temporal modulation of macrophage polarization. Selective activation of heat shock proteins 47 (Hsp47) and 70 (Hsp70) is shown to be critical for the above modulation. In the cranial defect healing model, surface potential and photothermal stimulation of the Gr/PVTF composite films can synergistically result in optimal bone regeneration, implying its potential application in the field of tissue regeneration. This work not only provides a new method for enhancing bone regeneration, but also delivers new insights into the modulation of cell behaviors through multiple physical cues.
研究领域:
生物材料
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组织工程
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再生医学
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生物医学工程
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纳米医学
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DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2025
·
IF 3
Song Peng,Yang-yang Sun,Qiangqiang Chu,Hua-dong Meng,Ming-wei Hao,Yan-bei Zhang
Background Leonurine (Leo) has antioxidant and anti-inflammatory activities. In this study, we investigated the effect of Leo in a rat model of lipopolysaccharide (LPS)-induced chronic obstructive pulmonary disease (COPD).Methods Rats with COPD were administered Leo, and the pulmonary function parameters, pathological changes, and inflammatory mediators in tissues were evaluated. The expression of IκBa, p65, JAK2, STAT3, p-IκBa, p-p65, p-JAK2 and p-STAT3 was measured using western blotting.Results Leo effectively improved the clinical manifestations of COPD by decreasing the pulmonary function parameters including peak expiratory flow and expiratory flow at 50% tidal volume, and improving pathological changes. Leo reduced lung inflammation and oxidative stress by reducing CD68+ cell infiltration, regulating Treg/Th17 cell differentiation, attenuating the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-17, increasing IL-10 secretion, and regulating malondialdehyde and glutathione peroxidase levels. In vitro experiments revealed that Leo exhibits similar inhibitory effects on Th17 cell differentiation and macrophage activation. Furthermore, Leo effectively protected against LPS-induced damage to bronchial airway epithelial cells by reducing reactive oxygen species production. Mechanistic investigations revealed Leo inhibits NF-κB transcriptional activity, downregulates the levels of p-p65, p-JAK2, and p-STAT3 without affecting their total protein levels.Conclusion Our results suggest that Leo exerts therapeutic effect against COPD. Leo inhibited tissue inflammation and oxidative stress in COPD rat models via inhibition of the NF-κB and JAK2/STAT3 signaling pathways.
研究领域:
呼吸医学
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药理学
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分子生物学
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炎症研究
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信号转导
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
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IF 6.5
Ziming Ren,Yuelei Zhang,Yanyan Liu,Gang Wang
Purpose The formation of biofilms hinders direct contact between antibiotics and bacteria, reducing the efficacy of antibiotic therapy and presenting a substantial obstacle to the treatment of chronic osteomyelitis. To address this problem, we successfully constructed a chemically and structurally robust vancomycin-copper-tannic acid (Van@CuTA) antibiotic sustained-release system via a simple synthetic method, to target bacteria and inhibit biofilm formation.Methods Tannic acid (TA), copper ions (Cu2+), and vancomycin hydrochloride (Van) were mixed and stirred at a low temperature to afford Van@CuTA nanospheres. Their antibacterial activity was evaluated against methicillin-resistant S. aureus (MRSA) using the Oxford cup method and live/dead bacterial staining. Their anti-biofilm activity was assessed via FE-SEM observations. Cell viability was assessed via MTT assay and osteogenic activity was detected via Western blotting (WB) and alkaline phosphatase (ALP) staining after co-culture with MG-63 cells. In vivo tibia-induced osteomyelitis model in rabbits was conducted to further validate the efficacy of Van@CuTA in treating osteomyelitis.Results The developed nanospheres exhibited drug release properties, with TA being released from the carrier and inhibiting the formation of bacterial biofilms. In vivo experiments demonstrated inhibition of MRSA biofilm formation through the encapsulation of TA within fibrin and its sustained release, followed by the sequential release of Van and Cu2⁺ to directly eradicate MRSA. Moreover, Van@CuTA effectively promoted cell proliferation and bone formation. Van@CuTA is a multifunctional system that integrates biofilm targeting, drug release, antimicrobial activity, and cuproptosis-like bacterial death.Conclusion This study offers a novel and promising strategy for the development of antimicrobial agents to combat MRSA-induced chronic osteomyelitis.
研究领域:
骨科学
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感染性疾病
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纳米医学
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抗菌材料
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药物递送系统
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
Advanced Biology
·
2025
·Vol. 9
·期 4
·2400512
·
IF 2.6
Xiaolong Zhang,Yushen Wang,Junlei Han,Weilong Zhao,Wenhong Zhang,Xinyu Li,Jun Chen,Wei Song,Li Wang
Heart disease remains a leading cause of mortality worldwide, posing a significant challenge to global healthcare systems. Traditional animal models and cell culture techniques are instrumental in advancing the understanding of cardiac pathophysiology. However, these methods are limited in their ability to fully replicate the heart's intricate functions. This underscores the need for a deeper investigation into the fundamental mechanisms of heart disease. Notably, cardiac pathology is often influenced by systemic factors, with conditions in other organs contributing to disease onset and progression. Cardiac-focused multi-organ chip technology has emerged to better elucidate these complex inter-organ communications and address the limitations of current in vitro models. This technology offers a novel approach by recreating the cardiac microenvironment and integrating it with other organ systems, thereby enabling more precise disease modeling and drug toxicity assessment. This review provides a comprehensive overview of the heart's structure and function, explores the advancements in cardiac organ chip development, and highlights the applications of cardiac-focused multi-organ chips in medical research. Finally, the future potential of this technology in enhancing disease modeling and therapeutic evaluation is discussed.
研究领域:
生物医学工程
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心血管研究
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药学科学
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组织工程
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微流控技术
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系统生物学
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PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 11
·445
·
IF 5.4
Junming Zhang,Jiangming Zhong,Yi Li,Qi Zhou,Zhiyun Du,Li Lin,Peng Shu,Ling Jiang,Wei Zhou
Background: Ultraviolet B (UVB) radiation induces oxidative stress, inflammation, and collagen degradation in skin, leading to photodamage. Ergosterol (ERG)—a sterol widely distributed in fungi and algae, including numerous marine species—possesses antioxidant and anti-inflammatory activities, but its photoprotective mechanisms remain unclear. Methods: Using integratedin vitro(UVB-irradiated human keratinocytes) andin vivo(topical ERG in a murine UVB model) approaches, combined with transcriptomic and network pharmacology analyses, we evaluated ERG’s effects on oxidative stress, inflammation, and extracellular matrix integrity. Results: ERG treatment preserved keratinocyte viability, reduced reactive oxygen species, and suppressed pro-inflammatory mediators after UVB exposure. In mice, topical ERG significantly attenuated epidermal hyperplasia, maintained tight-junction integrity, and inhibited collagen matrix degradation. Mechanistically, ERG exerted dual inhibition of the nuclear factor kappa B (NF-κB) pathway, which mediates inflammation, and the mitogen-activated protein kinase (MAPK) pathway, which regulates collagen degradation. Conclusions: These findings identify ERG as a marine-derived sterol with potent photoprotective activity that simultaneously targets oxidative stress, inflammation, and extracellular matrix damage, highlighting its promise as a natural compound for dermatological applications and aligning with ongoing efforts to explore marine-derived agents against skin oxidative stress and inflammation.
研究领域:
皮肤病学
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海洋天然产物
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药理学
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分子生物学
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氧化应激与炎症
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高影响因子
Journal of Cosmetic Dermatology
·
2025
·Vol. 24
·期 12
·e70468
·
IF 2.5
Miaohong Yang,Chaoyue Wang,Yaqi Yang,Ping Han,Ling Jiang,Shanpeng Chu,Guangling Yin,Lingna Xie,Jieqiong Chen,Xiaohui Yang,Zhiyun Du
Background Sensitive skin is characterized by impaired skin barrier function, inflammation and dryness, and the effects of existing treatments are limited. This study explored an oral prescription containing ceramides, proanthocyanidins, quercetin, and citrus flavonoids, which inhibit inflammation, enhance barrier function, and regulate the gut‐skin axis through a multi‐target mechanism to improve skin sensitivity. Methods The therapeutic effects of the oral prescription were evaluated using the ‐induced AD model and the AEW‐induced dry skin model. Key endpoints included skin lesion severity, TEWL, skin thickness, mast cell infiltration, inflammatory cytokine levels, and skin barrier protein expression. Microbial changes in gut flora were also assessed to evaluate the therapeutic effects of the gut‐skin axis on sensitive skin. Results In the AD model, oral high‐dose prescription (PG‐H) significantly improved skin lesions, reduced TEWL, epidermal thickness, and ear swelling, decreased mast cell infiltration and inflammatory factors (IL‐4/6/31, ET‐1), and enhanced barrier hydration. In the AEW model, PG‐H reduced TEWL, alleviated dryness and scaling, and upregulated the expressions of filaggrin, AQP3, and loricrin, indicating a restoration of skin barrier function and relief from skin dryness. Furthermore, PG‐H regulates the intestinal flora (with a reduction in Firmicutes/Bacteroides) and suggests potential therapeutic benefits for skin health. Conclusions The oral formulation containing ceramides, proanthocyanidins, quercetin, and citrus flavonoids improves skin barrier function, reduces inflammation, restores skin hydration, and modulates the skin‐gut axis through multi‐pathway and multi‐target mechanisms, effectively alleviating symptoms of atopic dermatitis and dry skin, thus highlighting its potential as a novel dietary supplement for treating sensitive skin and related conditions.
研究领域:
皮肤病学
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营养科学
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免疫学
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微生物组研究
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药理学
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DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
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IF 4.3
Huimin Li,Ziang Wang,Suwei He,Minghui Zhong,Xichen Wang,Weitao Hu,Jingrong Tang,Zhonghao Xiao,Xiaowen Shi,Zigang Cao
2-Hydroxyanthraquinone (2-hATQ), a photooxidation product of anthracene (ANT) within polycyclic aromatic hydrocarbons (PAHs), poses significant risks to ecological safety and human health. ANT is listed as a priority pollutant by the U.S. Environmental Protection Agency (EPA) due to its persistence and resistance to degradation in the environment. Consequently, 2-hATQ, inheriting these characteristics from its parent compound, is ubiquitously present in the environment and exhibits greater toxicity than ANT itself. However, research on its toxicological effects, particularly concerning cerebrovascular toxicity, remains limited. In this study, acute exposure of zebrafish embryos to various concentrations of 2-hATQ resulted in significant cerebrovascular developmental abnormalities, manifested as reduced total vascular area and decreased vessel number in the brain. Moreover, the number of brain microglia, reactive oxygen species (ROS) levels, and apoptotic cell counts were markedly increased. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that 2-hATQ disrupts zebrafish cerebrovascular and blood-brain barrier development by upregulating pro-inflammatory cytokines ( il1β , tnf-α , nf-κb , il6 ) and inhibiting the Wnt/β-catenin signaling pathway ( lef1 , β-catenin , dkk1 , wif1 ). The co-administration of dexamethasone or BML-284 effectively rescued the cerebrovascular damage. Furthermore, behavioral analysis demonstrated that exposed zebrafish larvae exhibited reduced locomotor activity and anxiety-like states. This study reveals for the first time the adverse effects of 2-hATQ exposure on brain vascular development in aquatic organisms, suggesting that 2-hATQ and its ANT-related derivatives may be potential risk factors for cerebrovascular diseases. Our findings reveal, for the first time, that 2-hATQ impairs cerebrovascular and BBB development through concurrent induction of inflammation and suppression of the Wnt/β-catenin pathway, identifying these as critical mechanistic events in its toxicity.
研究领域:
毒理学
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环境科学
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神经生物学
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发育生物学
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分子生物学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）