JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Qin Wang,Jiayu Jiang,Wenfei Chen,Hao Jiang,Zhirong Zhang,Xun Sun
Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis , but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block–poly (εcaprolactone) (PCL–PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8 mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL–PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL–PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders.
研究领域:
药理学
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风湿病学
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纳米技术
·
炎症
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Ping Sun,Qianqian Zhang,Wei Nie,Xiaojun Zhou,Liang Chen,Haibo Du,Shuguang Yang,Zhengwei You,Jiawen He,Chuanglong He
In the repair of large segmental bone defects, bone tissue is often unable to heal due to the destruction of the vascular network near the wound site. An ideal bone repair material should have both angiogenic and osteogenic capabilities. To achieve this goal, we used biodegradable mesoporous silica nanoparticles (MSNs) as a delivery vehicle for dexamethasone (DEX), a small-molecule drug that induces osteogenic differentiation. Subsequently, chitosan was covalently modified onto the surface of the nanoparticles by glycidoxypropyltrimethoxysilane (GPTMS) to construct nanoparticulate delivery systems (DEX@chi-MSNs) that induce osteoblast formation. The QK peptide, which mimics the α-helical structure of vascular endothelial growth factor (VEGF) binding to the receptor, was adsorbed to the surface of chitosan-modified MSNs nanoparticles (QK@chi-MSNs) to render them with angiogenic ability. The QK@chi-MSNs can promote the formation of the tubular structure of human umbilical vein endothelial cells (HUVECs) and angiogenesis in vivo, as demonstrated by a chicken embryo chorioallantoic test (CAM) and subcutaneous embedding test. The DEX@chi-MSNs can improve alkaline phosphatase (ALP) activity, mineralized nodule formation, and the expression of osteogenic-related genes and proteins by BMSCs. Furthermore, the ability of bone repair and angiogenesis was evaluated in a critical size skull defect model in rats by using nanocarriers loaded with both DEX and QK (QK/DEX@chi-MSNs). The results of computed tomography (CT) scan, histological examination, and immunofluorescence staining indicated that QK/DEX@chi-MSNs can promote bone formation and angiogenesis in vivo, which has broad application prospects in bone tissue engineering.
研究领域:
生物材料学
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再生医学
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组织工程学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Zihe Zhai,Wei Ouyang,Yuejun Yao,Yuqi Zhang,Haolan Zhang,Feng Xu,Changyou Gao
Acute lung injury (ALI) is associated with excessive inflammatory response, leading to acute respiratory distress syndrome (ARDS) without timely treatment. A fewer effective drugs are available currently to treat the ALI/ARDS. Herein, a therapeutic nanoplatform with reactive oxygen species (ROS)-responsiveness was developed for the regulation of inflammation. Dexamethasone acetate (Dex) was encapsulated into poly(thioketal) polymers to form polymeric nanoparticles (NPs) ( [email protected] ). The NPs were composed of poly(1,4-phenyleneacetonedimethylene thioketal) (PPADT) and polythioketal urethane (PTKU), in which the thioketal bonds could be cleaved by the high level of ROS at the ALI site. The [email protected] could accumulate in the pulmonary inflammatory sites and release the encapsulated payloads rapidly, leading to the decreased ROS level, less generation of pro-inflammatory cytokines, and reduced lung injury and mortality of mice. RNA sequencing (RNA-seq) analysis showed that the therapeutic efficacy of the NPs was associated with the modulation of many immune and inflammation-linked pathways. These findings provide a newly developed nanoplatform for the efficient treatment of ALI/ARDS.
研究领域:
药理学
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纳米技术
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炎症
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-13
·
IF 5.116
Chai Miaomiao,Gu Ce,Shen Qihua,Liu Jiaxing,Zhou Yi,Jin Ziyang,Xiong Wanli,Zhou Yan,Tan Wensong
Background and aim Inadequate vascularization is a challenge in bone tissue engineering because internal cells are prone to necrosis due to a lack of nutrient supply. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to construct prevascularized bone tissue in osteogenic induction medium (OIM) in vitro. The angiogenic capacity of HUVECs was limited in the coculture system. In this study, the effects of the components in the medium on HUVEC angiogenesis were analyzed. Methods The coculture system was established in OIM. Alizarin red staining and alkaline phosphatase staining were used to assess the osteogenic ability of MSCs. A Matrigel tube assay was used to assess the angiogenic ability of HUVECs in vitro. The proliferation of HUVECs was evaluated by cell counting and CCK-8 assays, and migration was evaluated by the streaked plate assay. The expression levels of angiogenesis-associated genes and proteins in HUVECs were measured by qRT-PCR and Western blotting, respectively. Results Dexamethasone in the OIM suppressed the proliferation and migration of HUVECs, inhibiting the formation of capillary-like structures. Our research showed that dexamethasone stimulated HUVECs to secrete tissue inhibitor of metalloproteinase (TIMP-3), which competed with vascular endothelial growth factor (VEGF-A) to bind to vascular endothelial growth factor receptor 2 (VEGFR2, KDR). This effect was related to inhibiting the phosphorylation of ERK and AKT, which are two downstream targets of KDR. However, under hypoxia, the enhanced expression of hypoxia-inducible factor-1α (HIF-1α) decreased the expression of TIMP-3 and promoted the phosphorylation of KDR, improving HUVEC angiogenesis in the coculture system. Conclusion Coculture of hypoxia-preconditioned HUVECs and MSCs showed robust angiogenesis and osteogenesis in OIM, which has important implications for prevascularization in bone tissue engineering in the future.
研究领域:
组织工程
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细胞生物学
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分子生物学
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Xue Wu,Lianyi Yang,Qing Chen,Ruijin Ran,Jun Cao,Ming Zhang
Experimental autoimmune uveitis (EAU) is a widely used model for noninfectious uveitis (NIU), a sight-threatening autoimmune ocular disease. Although glucocorticoids remain the first-line therapy, their short half-life and frequent administration increase the risk of systemic and ocular side effects. Here, we report the development of microenvironment-responsive hydrogels with drug-loaded microspheres for sustained dexamethasone acetate release: dexamethasone acetateloaded microspheres (DAMS) and polyethylene glycol (PEG) hydrogel-encapsulated microspheres (DAMS@Gel). Poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated and subsequently embedded in pH-responsive and injectable hydrogel formed via Schiff base crosslinking. The materials were then thoroughly characterized.In vitro, both DAMS and DAMS@Gel showed excellent biocompatibility with retinal pigment epithelial (ARPE-19) cells, as confirmed by reactive oxygen species (ROS), apoptosis, cell cycle, and cytotoxicity assays. In vivo safety was verified through subconjunctival injection in rabbits. In the rat EAU model, intravitreal administration of DAMS and DAMS@Gel significantly alleviated ocular inflammation, as evidenced by ocular inflammatory symptom observations, fundus imaging, histopathological examination, and decreased glial activation. This study demonstrated that the DAMS and DAMS@Gel drug delivery systems were successfully established and exhibited sustained release properties and stable characteristics. In vitro and in vivo assays indicated that the biological materials had excellent biocompatibility. In addition, both of DAMS and DAMS@Gel exerted therapeutic effects on EAU model rats, and intraocular inflammation was markedly reduced. This research may provide a theoretical foundation for the treatment of uveitis with DAMS and DAMS@Gel.
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DOI
PubMed
高影响因子
Theranostics
·
2017
·
IF 8.766
Jing-Bo Hu,Xu-Qi Kang,Jing Liang,Xiao-Juan Wang,Xiao-Ling Xu,Ping Yang,Xiao-Ying Ying,Sai-Ping Jiang,Yong-Zhong Du
The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis x antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DXM is incorporated into the micelles with 6.28 ± 0.21% drug loading content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to 48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to PEG-DXM micelles due to specific interaction between SA and E-selectin expressed on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can significantly ameliorate LPS-induced production of pro-inflammatory cytokines via suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM micelles show better therapeutical effects, as reflected by the improved renal function, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins.
研究领域:
药学
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纳米技术
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药理学
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炎症
·
肾脏生理
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 2
·1-11
·
IF 5.3
Huang Suiyuan,Sun Xuehua,Xin Jianwei,Ma Panpan,Zhang Yuqi,Cai Zhongyu,Wang Ji-Jiang
Dexamethasone sodium phosphate (DSP) and betamethasone sodium phosphate (BSP) imprinted hydrogels embedded with two-dimensional photonic crystals (2DPC) were developed as hormones-sensitive photonic hydrogel sensors with highly sensitive, selective, anti-interference and reproducible recognition capability. The DSP/BSP molecularly imprinted photonic hydrogels (denoted as DSP-MIPH and BSP-MIPH) can specifically recognize DSP/BSP by rebinding the DSP/BET molecules to nanocavities in the hydrogel network. This recognition is enabled by the similar shape, size, and binding sites of the nanocavities to the target molecules. The rebinding of hormones molecules causes the hydrogel to swell, resulting in a particle spacing increase of the embedded 2DPC of the hydrogel. The particle spacing increase can be used as sensing signal and can be acquired by simply measuring the Debye diffraction diameters of the photonic hydrogel sensor before and after exposure with a laser pointer and a ruler. The particle spacing increments of the DSP-MIPH and BSP-MIPH sensors linearly change when DSP and BSP concentrations changes within the ranges 0.025–1 μM, 10–100 μM, and 100–500 μM, and the limits of detection (LoD) are 21.8 nM for DSP and 12.6 nM for BSP, respectively. These photonic hydrogel sensors were successfully applied to the determination of DSP/BSP contents in the real pharmaceutical injections, providing an ideal strategy for the development of portable hormones sensors. Graphical
研究领域:
材料科学
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分析化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
·
IF 11.5
Xinni He,Wanchen Zhao,Huihui Xu,Hongluo Li,Minglong Chen,Yanping Fu,Shujin Liang,Shuling Li,Tingting Peng,Chao Lu,Xin Pan,Chuanbin Wu,Guilan Quan
Psoriasis is a prevalent relapsing dermatological condition that often necessitates lifelong treatment. The distinctive thickening of the stratum corneum presents a challenge to drug penetration. The employment of microneedles has been demonstrated to enhance the transdermal drug delivery efficacy by creating multiple microchannels in the skin. Nevertheless, polymeric microneedles often encounter difficulties in meeting the requirements for sustained drug release. It is imperative to acknowledge that sustained-release hydrogel microneedles are invariably fabricated under harsh crosslinking conditions. In addressing these challenges, a core-shell microneedles (CSMNs) system was customized at a facile, accessible process, enabling the in situ formation of supramolecular microhydrogels within the skin. This concept was realized by leveraging the interaction between the therapeutic drug dexamethasone sodium phosphate (DexP) and calcium chloride (CaCl 2 ), combined with the differential biphasic release technology (DexP HMNs). Upon insertion into the skin, the core of the microneedles rapidly released CaCl 2 , which diffused to the shell and formed a hydrogel with DexP, creating multiple reservoirs for the sustained release of DexP. In vitro transdermal permeation experiments demonstrated that DexP HMNs greatly prolonged the skin retention time of DexP. In the context of psoriasis treatment, DexP HMNs were demonstrated to be more effective than DexP CSMNs in inhibiting keratinocyte proliferation and significantly reducing the levels of inflammatory factors and immune cell infiltration at the lesion site. This study provides a new direction for the development of intelligent microneedle drug delivery systems for sustained drug release and enhanced management of chronic skin diseases.
研究领域:
药剂学
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皮肤病学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Qianwei Tang,Yanlin Chen,Meng Liu,Xueping Ning,Quanzhi Chen,Shengbin He
With excellent anti-inflammatory and immunomodulatory performances, dexamethasone (Dex) is widely used in the treatment of skin and mucosal ulcers. However, its therapeutic efficacy for oral ulcers is limited by the unique oral environment. To address this issue, we loaded dexamethasone into polylactic acid nanoparticles (PANs) and modified them with ligands to enhance their targeted delivery efficiency. These Dex-loaded PANs (Dex-PANs) were further incorporated into gelatin hydrogel to prolong the release of the drug with a single administration. A self-synthesized bisuccinimidyl-ester was used, for the first time, as the cross-linker to covalently adhere the gelatin hydrogel to the ulcer site, thereby resisting mechanical detachment or salivary erosion. Compared to the control group, the tensile strength of the cross-linked gelatin hydrogel adhesive on skin was increased by approximately 10-fold. Moreover, the gelatin hydrogel could maintain for over 5 days in saliva, during which it slowly degraded without detachment from the skin while releasing the Dex-loaded PANs. In vitro experiments demonstrated that the Dex-PANs incorporated in gelatin hydrogel exhibited no cytotoxicity and promoted the proliferation of gingival epithelial cells, accelerating ulcer healing. In vivo studies showed that the novel Dex formulation enabled rapid healing of oral ulcers with a single administration. This approach may contribute to advancements in medical adhesives and guide the creation of nanoparticle-based buccal delivery technologies.
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Lu Han,Hao Feng,Zhengchao Yuan,Muhammad Shafiq,Shuqi Lou,Mohamed El-Newehy,Meera Moydeen Abdulhameed,Yan Xiong,Xiaojing Zhao,Xiumei Mo,Jiafei Chen
Wound healing is often impeded by excessive inflammation and oxidative stress, necessitating multifunctional dressings with therapeutic and regenerative properties. Here, a biodegradable nanofiber dressing (PE@MD) composed of poly(L-lactide-co-ε-caprolactone) (PLCL), water-soluble eggshell membrane (ESM), and dexamethasone (DEX)-loaded mesoporous polydopamine nanoparticles (MPDA) was developed via electrospinning technology. Proteomic and metabolomic analyses revealed that ESM contains abundant proteins and metabolites associated with cytoskeletal organization, antioxidation, and modulation of inflammation, providing intrinsic bioactivity to the composite. The incorporation of MPDA enabled sustained and controlled DEX release while enhancing the ROS scavenging capacity. The optimized PE@MD nanofibers exhibited good flexibility, biocompatibility, and degradation properties. In vitro, the dressing promoted the migration of fibroblasts and endothelial cells, reduced ROS levels, and induced macrophage polarization toward the M2 phenotype through NF-κB inhibition. Transcriptomic analysis confirmed activation of antioxidant and extracellular matrix remodeling pathways. The PE@MD significantly accelerated wound closure, re-epithelialization, and collagen deposition while reducing COX-2, IL-1β, MPO, and NF-κB p65 expression in a rat full-thickness wound model. These findings demonstrate that the PE@MD dressing effectively integrates bioactive ESM and MPDA-mediated sustained drug release, providing a sustainable and multifunctional platform that promotes enhanced collagen deposition, accelerated re-epithelialization, and reduced inflammatory infiltration during skin repair.
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DOI
PubMed
高影响因子
Journal of Cleaner Production
·
2024
·
IF 9.7
Jin-Na Zhang,Xiao-Fan Gong,Guang-guo Ying,An-Guo Wang,Mei-Jun Dong,You-sheng Liu,Tong-Chu Deng,Mei-Ying Xu
In response to the widespread environmental concern of endocrine disruptors, our research investigated the aerobic biodegradation of dexamethasone (DEX), a widely used synthetic glucocorticoid with endocrine-disrupting properties, by strain Rhodococcus sp. D32. This innovative strain showcases remarkable DEX-degrading capabilities, with the half-life for degrading 500 μg/L DEX in MH broth being just 7.56 h. Utilizing high-resolution mass spectrometry, we identified six transformation products (TPs) and revealed a unique steroid nucleus-opening pathway marked by A-ring lactonization and subsequent lactone hydrolysis. This newly discovered pathway deviates from the classical steroid 9,10-seco pathways and previous transformations that preserved the intact steroid nucleus, thus expanding our knowledge of microbial steroid transformations. Additionally, the degradation process progressively converts the parent DEX into less ecotoxic products, significantly reducing the overall ecotoxicity of the system. This reduction remains evident when considering the combined toxicity of DEX and its TPs, indicating a promising approach for lessening environmental harm. Strain D32 also proved effective in various authentic aquatic environments, including fishpond water, urban sewage, river water, and reservoir water, where its introduction markedly expedited the dissipation of DEX. Our findings underscore the potential of strain D32 as a powerful tool for the bioremediation of DEX, presenting an efficient and eco-friendly strategy to alleviate the effects of this endocrine disruptor in aquatic ecosystems.
研究领域:
环境科学
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微生物学
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生物技术
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毒理学
✓ 已验证
DOI
高影响因子
Animal Models and Experimental Medicine
·
2025
·
IF 3.4
Dongcheng Wang,Xin Zhang,Zhen Wang,Cheng Ran,Jia Hao,Xiaobo Ma,Minghui Wang,Zhimin Zhou
Background Sudden sensorineural hearing loss (SSNHL), often associated with tinnitus, significantly impacts individuals' quality of life. Current treatments, such as free drugs via intravenous or intratympanic (IT) administration of dexamethasone (DEX) and lidocaine, face limitations like low bioavailability and rapid drug clearance. To address these challenges, we developed a local co-delivery system combining DEX microcrystals (DEX MCs) and lidocaine-loaded poly(lactic-co-glycolic acid) (PLGA) non-spherical microparticles (LPNMs) for sustained drug release in the inner ear. Methods DEX MCs and LPNMs were prepared using the traditional precipitation technique and double emulsion-solvent evaporation, respectively. After characterizing physicochemical properties and drug release kinetics, they were dispersed in sodium hyaluronate solution for IT injection, then in vivo pharmacokinetics and biocompatibility in guinea pigs were studied. Results DEX MCs exhibited stable dissolution, while LPNMs provided sustained lidocaine release, reducing potential side effects. In vivo studies in guinea pigs demonstrated prolonged drug retention in the perilymph and improved pharmacokinetics. Histological evaluation confirmed the good biocompatibility of this combined delivery system, with no significant inner ear damage observed. Conclusion This co-delivery system can be used as a depot for delivering both DEX and lidocaine to the inner ear and offers a promising approach for the synergistic treatment of SSNHL associated with tinnitus.
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PubMed
高影响因子
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