Materials Today Bio
·
2022
·
IF 10.761
Jiale Jin,Yang Liu,Chao Jiang,Yifan Shen,Guangyu Chu,Can Liu,Lejian Jiang,Guanrui Huang,Yifang Qin,Yijian Zhang,Chi Zhang,Yue Wang
Osteoarthritis (OA) is a common degenerative joint disease worldwide and currently there is no effective strategy to stop its progression. It is known that oxidative stress and inflammation can promote the development of OA, and therapeutic strategies against these conditions may alleviate OA. Arbutin (ARB), a major ingredient of the Chinese medicinal herb cowberry leaf, exerts good antioxidant and anti-inflammatory activities yet has not been studied in OA. Here we developed ARB-loaded gelatine methacryloyl-Liposome ( [email protected] ) microspheres which showed long-term release of ARB and excellent cartilage-targeting effects. The ARB-loaded microspheres effectively reduced the inflammatory response in interleukin (IL)-1β-treated arthritic chondrocytes. Moreover, the synthesized [email protected] microspheres regulated cartilage extracellular matrix (ECM) homeostasis through anti-inflammation effect via inhibiting NF-κB signaling and anti-oxidative stress effect via activating Nrf2 pathway. Intra-articular use of [email protected] can effectively reduce inflammation and oxidative stress in the articular cartilage and thus, attenuating OA progression in a mouse model. The study proposed a novel ARB-laden functional microsphere, [email protected] , and demonstrated that this compound may be used as an alternative therapeutics for treating OA.
研究领域:
药理学
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骨科
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Cheng-Ming Zhang,Yu-Xin Kang,Si-Yu Zheng,Yang Liu,Meng-Rou Liu,Gai-Ge Wu,Li Guo,Peng-Cui Li,Rui-Peng Zhao,Qian-Qian Duan,Shao-Wei Wang,Xiao-Chun Wei
Background Osteoarthritis (OA) is a progressive joint disorder marked by the degradation of cartilage. Elevated concentrations of hypoxia-inducible factor-2α (HIF-2α) are intricately linked to the pathological development of OA. PT2385 has demonstrated effective inhibition of HIF-2α, thereby potentially impeding the initial advancement of OA. Nevertheless, challenges persist, including limited penetration into the deeper layers of cartilage, issues related to charge rejection, and a heightened rate of clearance from the joint. These constraints necessitate further consideration and exploration. Methods It has been demonstrated that PT2385 exhibits efficient inhibition of HIF-2α expression, thereby contributing to the delay in the progression of osteoarthritis. The pH-responsive attributes of carbon quantum dots, specifically those employing m-phenylenediamine (m-CQDs) coated with bovine serum albumin (BSA), have been systematically evaluated. In both in vitro settings involving cartilage explants and in vivo experiments, the efficacy of BSA-m-CQDs-PT2385 (BCP) has been confirmed in facilitating the transport of PT2385 to the middle and deep layers of cartilage. Furthermore, the BCP system demonstrates controlled drug release contingent upon alterations in environmental pH. Results While the use of PT2385 alone provides protective effects on chondrocytes within an inflamed environment, there exists an opportunity for further enhancement in its efficacy when administered via intra-articular injection. The BCP formulation, characterized by appropriate particle size and charge, facilitates seamless penetration into cartilage tissue. Additionally, BCP demonstrates the capability to release drugs in response to changes in environmental pH. In vitro experiments reveal that BCP effectively inhibits Hif-2α expression and catabolic factors in chondrocytes. Notably, cartilage explants and in vivo experiments indicate that BCP surpasses PT2385 alone in inhibiting the expression of HIF-2α and matrix metalloproteinase 13, particularly in the middle and deep layers. Conclusions The BCP drug delivery system exhibits selective release of PT2385 in response to pH changes occurring during the progression of osteoarthritis (OA), thereby inhibiting HIF-2α expression deep within the cartilage. The use of BCP significantly augments the capacity of PT2385 to retard both cartilage degeneration and the progression of osteoarthritis. Consequently, BCP as an innovative approach utilizing m-CQDs to deliver PT2385 into articular cartilage, shows potential for treating osteoarthritis. This strategy opens new avenues for osteoarthritis treatment.
研究领域:
药学
·
生物医学工程
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骨科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-14
·
IF 6.518
Xiong Feng,Qin Zainen,Chen Haimin,Lan Qiumei,Wang Zetao,Lan Nihan,Yang Yuan,Zheng Li,Zhao Jinmin,Kai Dan
Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal − organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
JunWei Feng,Xia Deng,Peng Hao,ZongDong Zhu,Tao Li,XinWei Yuan,Jiang Hu,Yue Wang
Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.
研究领域:
生物医学工程
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材料科学
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骨科
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 44
·2206261
·
IF 19.924
Chao Li,Yawei Du,Hongzhi Lv,Jun Zhang,Pengzhen Zhuang,Wu Yang,Yingze Zhang,Juan Wang,Wenguo Cui,Wei Chen
Artemisinin and its derivatives (artemisinins) are first-line chemotherapeutic agents of lethal malaria, which also showed tremendous value in many other diseases including chronic inflammation. Unfortunately, almost all artemisinins are rapid-acting medicines with an extremely short half-life in vivo, which significantly limits their clinical application for these new adaptation diseases. In this study, a locally injectable long-acting gene/artemisinin co-delivery nano-microplex consisting of a biodegradable hyaluronic acid (HA) microsphere and releasable gene/artemisinin co-delivery nano-lipoplex is developed first, to obtain an improved efficacy for rheumatoid arthritis (RA). Briefly, a cationic multicomponent drug-embedded liposome with pharmacological activity is first reported based on two novel artemisinin derivatives (dAPC and dACC), which possess mimic phospholipids and cationic lipids, respectively. A cationic artemisinin-embedded lipoplex is first reported as a medicative gene carrier here. An in situ injectable TNF-α siRNA/artemisinin co-delivery nano-microplex (MTAsi@MG) is further prepared by immobilization of TNF-α siRNA/lipoplex on porous microfluidic HA microspheres. Using this nano-microplex for intra-articular injection, the sustaining activity of gene therapy and artemisinin efficacy for RA long-term treatment is first realized. Undoubtedly, this intra-articular injectable TNF-α siRNA/artemisinin co-delivery nano-microplex based on dAPC/dACC lipoplex and microfluidic microspheres would be one of the most potent gene/drug co-delivery systems for RA therapy.
研究领域:
药学
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生物技术
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纳米医学
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风湿病学
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分子生物学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Qi Wan,Hui Chen,Guirun Xiong,Rui Jiao,Yun Liu,Xiaolei Li,Yu Sun,Jingcheng Wang,Lianqi Yan
Intraarticular fibrosis following knee surgery is a troublesome complication and remains a challenging problem for clinicians. Artesunate (ART), a classical anti-malarial drug extracted from the Chinese medicinal herb Artemisia annua L, has been associated with some fibrosis-related diseases. However, its effect and underlying mechanism on knee arthrofibrosis are still obscure. In the present study, we found that ART induced cellular autophagy flux and inhibited cell proliferation in fibroblasts. Intriguingly, genetic depletion of Beclin-1 abolished ART-triggered cellular autophagy and further attenuated the inhibitory effect of ART on fibroblasts proliferation. Moreover, at molecular level, our results demonstrated that ART-induced autophagy activation was associated with the inhibition of mTOR signaling through PI3K/AKT/mTOR pathway and AMPK/mTOR pathway. In vivo, ART treatment triggered autophagy activation and alleviated the severity of surgery-induced knee arthrofibrosis. Taken together, we concluded that ART exhibited anti-proliferation efficacy in fibroblasts and alleviated the severity of knee arthrofibrosis in rabbits by inducing Beclin-1-mediated autophagy via inhibition of mTOR signaling. These findings indicated that ART might be a potential therapeutic agent for preventing the progression of surgery-induced intraarticular fibrosis of knee.
研究领域:
药理学
·
骨科
·
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
Tissue Engineering and Regenerative Medicine
·
2021
·Vol. 18
·期 1
·113-125
·
IF 4.169
Mou Donggang,Yu Qunying,Zhang Jimei,Zhou Jianping,Li Xinmin,Zhuang Weiyi,Yang Xuming
Background: Pain and cartilage destruction caused by osteoarthritis (OA) is a major challenge in clinical treatment. Traditional intra-articular injection of hyaluronic acid (HA) can relieve the disease, but limited by the difficulty of long-term maintenance of efficacy. Methods: In this study, an injectable and self-healing hydrogel was synthesized by in situ crosslinking of N -carboxyethyl chitosan ( N -chitosan), adipic acid dihydrazide (ADH), and hyaluronic acid–aldehyde (HA-ALD). Results: This supramolecular hydrogel sustains good biocompatibility for chondrocytes. Intra-articular injection of this novel hydrogel can significantly alleviate the local inflammation microenvironment in knee joints, through inhibiting the inflammatory cytokines (such as TNF-α, IL-1β, IL-6 and IL-17) in the synovial fluid and cartilage at 2- and even 12-weeks post-injection. Histological and behavioral test indicated that hydrogel injection protected cartilage destruction and relieved pain in OA rats, in comparison to HA injection. Conclusion: This kind of novel hydrogel, which is superior to the traditional HA injection, reveals a great potential for the treatment of OA.
研究领域:
骨科
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生物材料
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药理学
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Dongze Wu,Shuhui Yang,Zhe Gong,Xinxin Zhu,Juncong Hong,Haitao Wang,Wenbin Xu,Juncheng Lai,Xiumei Wang,Jiye Lu,Xiangqian Fang,Guoqiang Jiang,Jinjin Zhu
Osteoarthritis (OA) is characterized by symptoms such as abnormal lubrication function of synovial fluid and heightened friction on the cartilage surface in its early stages, prior to evident cartilage damage. Current early intervention strategies employing lubricated hydrogels to shield cartilage from friction often overlook the significance of hydrogel-cartilage adhesion and enhancement of the cartilage extracellular matrix (ECM). Herein, we constructed a hydrogel based on dihydrazide-modified hyaluronic acid (HA) (AHA) and catechol-conjugated aldehyde-modified HA (CHA), which not only adheres to the cartilage surface as an effective lubricant but also improves the extracellular environment of chondrocytes in OA. Material characterization experiments on AHA/CHA hydrogels with varying concentrations validated their exceptional self-healing capabilities, superior injectability and viscoelasticity, sustained adhesion strength to cartilage, and a low friction coefficient. Chondrocytes exhibited robust adhesion and proliferation on the AHA/CHA hydrogel surface, with the upregulation of cartilage matrix protein expression. Intra-articular injection of AHA/CHA hydrogels was performed following destabilization of the medial meniscus (DMM) surgery in mice to assess its protective effect on cartilage. The AHA/CHA hydrogel effectively attenuated the degree of cartilage wear, facilitated chondrocytes' anabolic metabolism, and restored the ECM of cartilage. Therefore, the AHA/CHA hydrogel emerges as a promising therapeutic approach in clinical practices of OA treatment.
研究领域:
生物医学工程
·
骨科
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Ruiyuan Zhang,Fang Liu,Qian Zhang,Luping Yang,Xinlian Hou,Taoming Du,Jie Fan,Huiling Hu,Hongdan Deng,Li Hao,Li Guo,Chaomei Fu
The polysaccharides (FP) extracted from the lateral roots of Aconitum carmichaelii Debx. (Fuzi) are natural compounds, which have effective therapy for rheumatoid arthritis (RA). Methotrexate (MTX) is the first-line drug for RA, but its application is greatly limited to the toxicity in liver and kidney and drug resistance. In this study, an attempt is made to apply oxidized FP (OFP) as a polymer carrier based on intra-articular delivery system loaded MTX. The FP could be modified and used as comprehensive gel carriers with biocompatibility and degradability for therapy of RA. Firstly, OFP−chitosan−poloxamer 407 in situ gel (OFP−CS−F407−MTX gel) was prepared by natural non-toxic cross-linking agents. Physicochemical characterization was performed by using 1 H NMR and FTIR spectroscopic techniques to assess the successful functionalization of OFP. TGA, SEM and rheological experiment of OFP−CS−F407−MTX gel were investigated. Notably, we loaded MTX into OFP−CS−F407−MTX gel which had remarkable therapeutic efficacy and biosafety for RA. Therefore, OFP−CS−F407−MTX in situ gel delivery system can potentially reduce systemic toxicity and irritation of oral administration of MTX but hold a controlled release of drug for a long period of time.
研究领域:
药学
·
风湿病学
·
材料科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chenxi Li,Rui Liu,Yurong Song,Youwen Chen,Dongjie Zhu,Liuchunyang Yu,Qingcai Huang,Zhengjia Zhang,Zeyu Xue,Zhenglai Hua,Cheng Lu,Aiping Lu,Yuanyan Liu
Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by synovial inflammation in multiple joints. Triptolide (TP) is a disease-modifying anti-rheumatic drug (DMARD) highly effective in patients with RA and has anti-inflammatory properties. However, its clinical application has been limited owing to practical disadvantages. In the present study, hyaluronic acid (HA) hydrogel-loaded RGD-attached gold nanoparticles (AuNPs) containing TP were synthesized to alleviate the toxicity and increase therapeutic specificity. The hydrogels can be applied for targeted photothermal-chemo treatment and in vivo imaging of RA. Hydrogel systems with tyramine-modified HA (TA-HA) conjugates have been applied to artificial tissue models as surrogates of cartilage to investigate drug transport and release properties. After degradation of HA chains, heat was locally generated at the inflammation region site due to near-infrared resonance (NIR) irradiation of AuNPs, and TP was released from nanoparticles, delivering heat and drug to the inflamed joints simultaneously. RA can be penetrated with NIR light. Intraarticular administration of the hydrogels containing low dosage of TP with NIR irradiation improved the inflamed conditions in mice with collagen-induced arthritis (CIA). Additionally, in vitro experiments were applied to deeply verify the antirheumatic mechanisms of TP-PLGA-Au@RGD/HA hydrogels. TP-PLGA-Au@RGD/HA hydrogel treatment significantly reduced the migratory and invasive capacities of RA fibroblast-like synoviocytes (RA-FLS) in vitro , through the decrease of phosphorylation of mTOR and its substrates, p70S6K1, thus inhibiting the mTOR pathway.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL AND MOLECULAR MEDICINE
·
2025
·
IF 12.9
Yang Qihao,Wu Jianqun,Huang Songqiang,Zeng Jing,Jing Yihan,Wang Zhiyong,Zhang Chi,Wu Zenghui,Liu Song,Wang Zhao
Here we investigate the effects and mechanisms of eicosapentaenoic acid (EPA) in regulating chondrocyte mechanics during inflammation in the progression of osteoarthritis (OA). Primary porcine chondrocytes and human OA chondrocytes were isolated and cultured. Cell mechanical properties were measured using atomic force microscopy. RNA sequencing, immunocytochemistry, quantitative PCR and western blotting were used to elucidate associated signaling mechanisms. Porcine cartilage and human OA cartilage explants were collected. Human articular cartilage samples were obtained from ten donors. Anterior cruciate ligament transection surgery was performed to induce OA in male C57BL/6J mice. The therapeutic effects of EPA and activation of associated signaling were evaluated using histology, immunohistochemistry and micro-computed tomography. EPA reduced F-actin intensity and Young’s modulus in IL-1α-treated porcine chondrocytes and in human OA chondrocytes. Mechanistically, EPA inhibited IL-1α-induced increase in CD44 expression in porcine chondrocytes by suppressing phosphorylation of NF-κB subunits p65. In addition, EPA alleviated articular cartilage degeneration and decreased the expression of p-p65 and CD44 in IL-1α-treated porcine and human OA cartilage explants. Moreover, EPA suppressed the increase in Young’s modulus induced by CD44 ligands (A6 peptide and low-molecular-weight hyaluronic acid) in porcine chondrocytes. Finally, intraarticular injection of EPA emulsion-integrated hyaluronic acid injection attenuated OA-associated alterations in articular cartilage and subchondral bone and decreased CD44 expression in mice. Our data not only provide new insights into EPA’s chondroprotective actions and underlying mechanisms but also offer new evidence supporting the therapeutic efficacy of a novel EPA emulsion-integrated hyaluronic acid injection for OA treatment.
研究领域:
风湿病学
·
分子生物学
·
生物力学
·
骨科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Guangyong Lin,Huirong Huang,Meng Sun,Zhinan He,Shengjie Li,Xindan Liang,Yuqi Yan,Chenyu Qiu,Shize Li,Xinyu Zhao,Wanling Zhu,Longfa Kou,Ruijie Chen
Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a "two-stage" drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.
研究领域:
药学
·
生物医学工程
·
骨科
·
纳米技术
·
药物递送
✓ 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）