INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
·
IF 6
Yuanyuan Liu,Yuanyao Lin,Xuemei He
An ultrasound-responsive PLGA nanosystem co-encapsulating CXB, CAT, and PFP was developed. • Ultrasound triggered PFP phase transition and promoted on-demand CXB release from nanoparticles. • CAT retained catalytic activity and enabled oxygen generation, helping alleviate tumor hypoxia. • The nanosystem potentiated the antitumor activity of imatinib against GIST in vitro and in vivo. • Combined treatment increased apoptosis and suppressed migration and tumor growth in GIST. The therapeutic efficacy of imatinib (IM) in gastrointestinal stromal tumors (GISTs) is often limited by inadequate intratumoral drug accumulation and an abnormal tumor microenvironment. In this study, an ultrasound-responsive poly(lactic-co-glycolic acid) (PLGA) nanoparticle system, designated CXB/CAT@PFP-PLGA NPs, was developed for the co-delivery of celecoxib (CXB) and catalase (CAT) to enhance the antitumor efficacy of IM. The nanoparticles were characterized in terms of their physicochemical properties, ultrasound responsiveness, and oxygen-generating capability. Their ability to potentiate IM therapy was evaluated both in vitro and in vivo, while biodistribution and biosafety were assessed in vivo. The results showed that CXB/CAT@PFP-PLGA NPs exhibited a relatively uniform size distribution and successfully co-encapsulated CXB and CAT. Upon ultrasound irradiation, the nanoparticles underwent phase transition, thereby triggering drug release. In vitro, CXB/CAT@PFP-PLGA NPs enhanced the inhibitory effect of IM by reducing cell viability, promoting apoptosis, and inhibiting cell migration. In vivo, the nanosystem improved the antitumor efficacy of IM, accumulated at the tumor site, suppressed tumor growth, and showed no evident systemic toxicity. Collectively, these findings suggest that CXB/CAT@PFP-PLGA NPs may represent a promising strategy for enhancing IM therapy in GIST. Download: Download high-res image (89KB) Download: Download full-size image
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高影响因子
BMC Pharmacology & Toxicology
·
2022
·Vol. 23
·期 1
·1-14
·
IF 2.605
Chen Weisin,Yasen Miersalijiang,Wang Hanquan,Zhuang Chenyang,Wang Zixiang,Lu Shunyi,Jiang Libo,Lin Hong
Background Intervertebral disc degeneration results from a variety of etiologies, including inflammation and aging. Degenerated intervertebral discs feature down-regulated extracellular matrix synthesis, resulting in losing their ability to retain water and absorb compression. Celecoxib is a well-known selective cyclooxygenase-2 inhibitor for treating arthritis and relieving pain. Nevertheless, the mechanism of Celecoxib for treating inflammation-related intervertebral disc degeneration has not yet been clarified.MethodProtein synthesis was analyzed by western blot. Fluorescent probes DCFH-DA and MitoSox Red detected reactive oxygen species and were measured by flow cytometry. The activity of the kinase pathway was evaluated by protein phosphorylation. Autophagy was monitored by mRFP-GFP-LC3 transfection and LC3 analysis. Mitochondrial apoptotic proteins were analyzed by western blot and cell membrane integrity was measured by flow cytometry. The autophagic gene was silenced by siRNA.Results In this study, interleukin-1β stimulation reduced the synthesis of aggrecan, type I and II collagen and caused excessive production of reactive oxygen species. We looked for a therapeutic window of Celecoxib for nucleus pulposus cells to regain extracellular matrix synthesis and reduce oxidative stress. To look into nucleus pulposus cells in response to stimuli, enhancement of autophagy was achieved by Celecoxib, confirmed by mRFP-GFP-LC3 transfection and LC3 analysis. The mammalian target of rapamycin and a panel of downstream proteins responded to Celecoxib and propelled autophagy machinery to stabilize homeostasis. Ultimately, inhibition of autophagy by silencing autophagy protein 5 disrupted the protective effects of Celecoxib, culminating in apoptosis.Conclusion In summary, we have demonstrated a new use for the old drug Celecoxib that treats intervertebral disc degeneration by enhancing autophagy in nucleus pulposus cells and opening a door for treating other degenerative diseases.
研究领域:
药理学
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细胞生物学
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骨科
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分子生物学
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PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
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2024
·Vol. 57
·期 10
·1627-1636
·
IF 0.8
Liu Lang,Ouyang Fenfen,Li Ting,Wen Min,Zha Guodong,Chen Libo,Fu Xue,Zhu Li qing
Celecoxib, the first cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug, has a wide range of pharmacological effects, including anti-inflammatory, antirheumatic and antitumor effects. However, celecoxib’s poor solubility severely limits its clinical application. Thus, a novel ternary solid dispersion system was developed using PVP K30 and hydroxypropyl-β-cyclodextrin (HPβCD) as carrier materials in order to improve its solubility and dissolution behavior. The solid dispersion system was characterized by SEM, XRD, FT-IR, DSC, in vitro dissolution, saturated solubility, and contact angle test; the stability of the samples under extreme environments was investigated as well. The results showed that the novel ternary solid dispersion doped with PVP K30 and HPβCD has enhanced solubility around 6.28-fold, an almost 13.94-fold increase in the dissolution rate (120 min) compared with celecoxib’s active pharmaceutical ingredient. The substantial improvement in its dissolution performance is attributed to the fact that celecoxib is dispersed in the carrier material in an amorphous form and has hydrogen bonding interactions with the carrier materials. In addition, the improvement of wettability is one of the reasons for its increased solubility. In conclusion, the combination of PVP K30 and HPβCD can significantly improve the solubility of celecoxib and this novel solid dispersion system provides new ideas and methods to further improve the solubility of insoluble drugs.
研究领域:
药剂学
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药物技术
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药物传递
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材料科学
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生物药剂学
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Fancan Wu,Wanyou He,Da Song,Zhen Wu,Peng Dai,Xueqin Zheng,Hanbing Wang,Chao Xie
Chronic pain is a prevalent condition affecting a significant portion of the global population and is known to be associated with an increased risk of cardiovascular diseases. Despite the clinical relevance, the mechanisms underlying the link between chronic pain and myocardial ischemia-reperfusion (MI/R) injury remain poorly understood. This study aimed to investigate the role of the superior cervical ganglion (SCG) in mediating the effects of chronic pain on MI/R injury and to develop a novel therapeutic strategy. We identified that chronic pain upregulated TNF-α expression and induced hyperactivity in SCG sympathetic neurons, exacerbating MI/R injury. To address this, we engineered an injectable Pluronic/alginate-based composite hydrogel loaded with celecoxib and ropivacaine (celecoxib@Laponite-dopamine-alginate-Pluronic F-127@ropivacaine, CLDAFR). This hydrogel was designed to target the SCG, providing a localized and sustained release of the therapeutic agents, thereby mitigating neuronal inflammation and inhibiting neuronal hyperactivity. The CLDAFR hydrogel demonstrated excellent biocompatibility, heat-sensitive gelation properties, and controlled drug release in vitro. In vivo studies showed that applying CLDAFR effectively reduced MI/R injury in a chronic pain model by suppressing TNF-α expression and SCG neuronal activity. In conclusion, the CLDAFR hydrogel represents a promising therapeutic material for treating chronic pain-exacerbated MI/R injury by precisely targeting the SCG and providing a sustained anti-inflammatory and analgesic effect.
研究领域:
药理学
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心脏病学
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材料科学
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神经科学
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PubMed
高影响因子
Drug Delivery and Translational Research
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2026
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IF 6.9
Yuan Hao,Zhang Bingwen,Sun Wen,Liu Haofan,Hu Liandong
In this study, celecoxib (CXB) microspheres (CM) and ropivacaine (RPV) microspheres (RM) were prepared respectively. A poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol)-block-poly (D, L-lactide-co-glycolide) (PLGA–PEG–PLGA, PPP) was synthesized by copolymerizing glycolide and lactide with polyethylene glycol. CM, RM, and hydroxyapatite (HA) were then incorporated into PPP solution to construct the microsphere–hydrogel system (CRMH hydrogels). CM, RM, and CRMH were systematically characterized in terms of morphology, physicochemical properties, pH-buffering capacity, and degradation behavior. The pH-dependent drug release and release kinetics of the individual CM, RM and the CRMH hydrogels were also investigated. In vitro release studies demonstrated that CRMH hydrogels provided coordinated, sustained release of CXB and RPV at pH 6.2. In a rabbit osteoarthritis (OA) model, intra-articular (IA) administration of CRMH hydrogels achieved sustained drug retention and release within the joint cavity, and effectively promoted articular cartilage repair. Overall, the CRMH hydrogels showed promising synergistic therapeutic potential for OA.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-19
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IF 10.6
Zhang Xiaojie,Liang Qiangwei,Cao Yongjin,Yang Ting,An Min,Liu Zihan,Yang Jiayu,Liu Yanhua
Myeloid-derived suppressor cells (MDSCs) have played a significant role in facilitating tumor immune escape and inducing an immunosuppressive tumor microenvironment. Eliminating MDSCs and tumor cells remains a major challenge in cancer immunotherapy. A novel approach has been developed using gemcitabine-celecoxib twin drug-based nano-assembled carrier-free nanoparticles (GEM-CXB NPs) for dual depletion of MDSCs and tumor cells in breast cancer chemoimmunotherapy. The GEM-CXB NPs exhibit prolonged blood circulation, leading to the preferential accumulation and co-release of GEM and CXB in tumors. This promotes synergistic chemotherapeutic activity by the proliferation inhibition and apoptosis induction against 4T1 tumor cells. In addition, it enhances tumor immunogenicity by immunogenic cell death induction and MDSC-induced immunosuppression alleviation through the depletion of MDSCs. These mechanisms synergistically activate the antitumor immune function of cytotoxic T cells and natural killer cells, inhibit the proliferation of regulatory T cells, and promote the M2 to M1 phenotype repolarization of tumor-associated macrophages, considerably enhancing the overall antitumor and anti-metastasis efficacy in BALB/c mice bearing 4T1 tumors. The simplified engineering of GEM-CXB NPs, with their dual depletion strategy targeting immunosuppressive cells and tumor cells, represents an advanced concept in cancer chemoimmunotherapy. Graphical Abstract
研究领域:
癌症免疫治疗
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纳米技术
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药学
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肿瘤学
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免疫学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2025
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IF 5.4
Xiangyun Tan,Yuan Yang,Junjie Hu,Yan Meng,Liang Chen,Guohua Zheng,Han Xiao,Zhenpeng Qiu
Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with insidious onset, limited treatments, and poor prognosis. Recent studies show celecoxib exerts marked cytotoxic effects on cholangiocarcinoma cell lines, suggesting its potential as an iCCA therapy. However, the potential molecular and cellular mechanisms that link celecoxib treatment to its toxicological outcomes remain unclear. In this study, we induced iCCA in mice by overexpressing AKT and YapS127A (hereafter referred to as AKT/YapS127A) and administered celecoxib continuously to evaluate its antitumor effects in vivo . The results demonstrate that celecoxib effectively inhibited tumor growth in AKT/YapS127A-driven iCCA mice. Mechanistically, celecoxib boosted levels of cell cycle inhibitors p21 Waf1/Cip1 and p27 Kip1 , leading to cell cycle arrest. It also promoted apoptosis by downregulating the expression of anti-apoptotic proteins Mcl-1 and Bcl-2. These effects were associated with the modulation of the AKT/mTORC1 signaling pathway. Consistently, celecoxib recapitulated AKT/mTORC1 inhibition and subsequent cell cycle/apoptotic regulator alterations in iCCA cell lines. Collectively, our study elucidates the molecular mechanisms through which celecoxib exerts its anti-tumor effects in iCCA, demonstrating its capacity to induce cytotoxic outcomes via the precise regulation of the AKT/mTORC1 pathway. These findings deepen understanding of the toxicological actions of celecoxib and provide critical insights for developing targeted iCCA therapies.
研究领域:
肿瘤学
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药理学
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分子生物学
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肝病学
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细胞信号传导
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Xin Zhao,Shibin Han,Cheng Chen,Xiaoyi Lv,Jiahe Li,Chen Chen
Celecoxib (CXB) is a non-steroidal anti-inflammatory drug used to prevent and treat arthritis. However, overdosing or improper use can cause adverse reactions. SERS is an important tool for therapeutic drug monitoring (TDM).The present study proposes an innovative detection scheme based on SERS deep learning, aiming to achieve qualitative identification and quantitative detection of CXB at the Raman spectrum level. In this paper, a composite SERS substrate consisting of silver (Ag)@ platinum (Pt)@ porous silicon Bragg mirror (PSB) was synthesized. Crystal violet (CV) was used as probe to characterize the substrate properties, and the substrate showed excellent SERS properties and long-term stability. The substrate significantly enhanced the SERS response capacity to CXB, showing excellent reproducibility and high sensitivity. The LOD and the recovery rate were both within the reasonable range when the substrate was used to detect CXB concentration in serum. Three deep learning models, GoogleNet, ResNet and VGG, were used to classify five kinds of blood drug concentrations. Among them, the GoogleNet model based on spectral dataset achieved the highest classification accuracy of 84.17 %. The deep learning-SERS integrated system supports blood drug concentration discrimination, helping doctors personalize treatment strategies for arthritis patients and improving clinical efficiency.
研究领域:
分析化学
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生物医学工程
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药物分析
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纳米材料
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医疗人工智能
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2020
·
IF 3.616
Jiahui Sun,Jing Li,Qi Liu,Min Jiang,Mengjia Yang,Siwen Zhan,Tong Qiu,Kaiyong He,Xueqiong Zhang
This study aimed to develop, evaluate, and optimize the mPEG-PLA/vitamin E-TPGS mixed micelle drug delivery system to encapsulate celecoxib (CXB) and honokiol (HNK) for intravenous treatment of breast cancer. To this end, we formulated CXB-loaded mPEG-PLA/vitamin E-TPGS (PV-CXB) and HNK-loaded mPEG-PLA/vitamin E-TPGS (PV-HNK) mixed micelles and analyzed their characteristics. The 4T1 cell line was used for cytotoxicity determination and cellular uptake experiments, and for establishing a 4T1-bearing mouse model for histopathology, immunofluorescence, terminal deoxynucleotidyl transferase-mediated nick end labeling, and Western blot analysis . The synergistic effects of PV-CXB and PV-HNK combination therapy were investigated in vitro and in vivo using the coefficient of drug interaction values. The mean size of PV-CXB and PV-HNK prepared with optimal formulation was approximately 50 nm , with a spherical shape. PV-CXB and PV-HNK combination therapy exhibited cytotoxicity in 4T1 cells in vitro. However, the toxicity of PV-CXB and PV-HNK combination therapy was not apparent in normal tissues (heart, liver, spleen, lung, and kidney) in vivo and reduced the expression of collagen fibers in tumor tissues. Moreover, the combination therapy reduced the expression of tumor growth biomarkers (Foxp3, CD4, Gr-1, CD11b, CD31, Ki67, FoxM1, and VEGF). In addition, the tumor cell apoptosis rate reached 45.71 ± 0.62%. The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo. Thus, the PV-CXB and PV-HNK drug delivery system could be used as a potential combination therapy for breast cancer .
研究领域:
药剂学
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肿瘤学
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生物医学工程
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PubMed
高影响因子
AAPS PHARMSCITECH
·
2016
·Vol. 18
·期 3
·729-737
·
IF 1.954
Li Yongquan,Xiao Yu,Yin Zongning
As an effective COX-2 inhibitor, celecoxib is widely used in anti-inflammation therapy. However, it may cause cardiovascular risks and renal adverse effects. In the present study, we aimed to construct a celecoxib prodrug with enhanced anti-inflammatory efficacy and reduced adverse effects using folate in order to target activated macrophages. Folate-glycine-celecoxib was synthesized and identified by 1 H-NMR, MS, and FTIR analyses. The cytotoxicity of folate-glycine-celecoxib was tested on murine macrophage cells (RAW264.7) using thiazolyl blue tetrazolium bromide. Cellular uptake studies were employed to determine targeting ability toward folate receptors via flow cytometry and confocal microscopy. Anti-inflammatory efficacy of folate-glycine-celecoxib was investigated by measuring the concentration of LPS-induced nitric oxide (NO). Folate-glycine-celecoxib exhibited lower cytotoxicity than conventional celecoxib, and this conjugate could be targetedly transported into RAW264.7 cells through binding with folate receptors on cell surface. Through targeting to RAW264.7 cells, folate-glycine-celecoxib exhibited better effects than equimolar celecoxib in NO inhibition, suggesting greater anti-inflammatory activity. These findings demonstrated that the prodrug folate-glycine-celecoxib had potential to treat inflammatory disease with low cytotoxicity and high targeting ability.
研究领域:
药理学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2022
·
IF 5.016
Jian Li,Xin Tian,Kang Wang,Yong Jia,Fuguang Ma
Dissolving microneedles, the promising vehicles for transdermal delivery, are incapable of directly loading hydrophobic components that limit the application of transdermal drug delivery. Microemulsion holds great potential in the solubilisation of water-insoluble drugs but is limited by the high epidermal retention. In this study, we fabricated microemulsion-incorporated dissolving microneedles co-loading celecoxib and α-linolenic acid (Cel-MEs@MNs) for enhancing osteoarthritis (OA) therapy via synergistic anti-inflammation and potent transdermal delivery. Cel-MEs@MNs composed of celecoxib & α-linolenic acid-coloaded microemulsion (Cel-MEs) and hyaluronic acid-based microneedles (MNs) can be completely dissolved in 90 s with a particle size of ∼30 nm. Each microneedle array with a hardness exceeding 30 N contained 57.9 ± 2.5 μg of celecoxib and 442.5 ± 24.2 μg of α-linolenic acid. The 8 h-cumulative transdermal of celecoxib from Cel-MEs@MNs was 89.2 ± 5.1 μg celecoxib/cm2, which is 2.98-fold higher than that from Cel-MEs. Combinational celecoxib and α-linolenic acid with a weight ratio of 1/5 can synergistically induce M1-like macrophage to M2 repolarization, reduce M1-like macrophages-resulted chondrocytes apoptosis, and lower serum prostaglandin E-2 (PGE-2). Notably, Cel-MEs@MNs amplified such collaborated anti-inflammatory effects. More importantly, in the treatment of OA-bearing rat models, Cel-MEs@MNs with a half-dose of celecoxib and α-linolenic acid significantly shrunk the paw swelling, reduced inflammatory cytokines, and improved cartilage damage compared with the oral administration of celecoxib and α-linolenic acid, as well as transdermal administration of Cel-MEs. Such an integrational strategy of microemulsion-incorporated dissolving MNs offers the feasibility of combinational celecoxib and α-linolenic acid in transdermal permeation and boosted OA therapy.
研究领域:
药剂学
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药物递送系统
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药理学
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骨科
·
炎症
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产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2025
·Vol. 26
·期 1
·1-14
·
IF 4
Fan Fan,Zhou Feng,Zhang Jiayu,Yang Junhui,Zhuang Kai,Shan Yudong,Jiang Lei,Zhang Jiantao
Amorphous solid dispersion (ASD) is one of the most studied strategies for improving the dissolution performance of poorly water-soluble drugs, but ASDs often have low drug loadings, thereby necessitating larger dosage sizes. This study intended to create Soluplus® (SOL)-based microparticle ASDs with high drug loading (up to 60 w/w%) and long-term stability (at least 16 months) using electrospraying to enhance the dissolution of poorly water-soluble celecoxib (CEL). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed that the electrosprayed SOL-CEL microparticles were amorphous, and Fourier transform infrared spectroscopy (FTIR) data indicated the presence of hydrogen bonding between SOL and CEL in the microparticles, which helped stabilize the ASDs. In vitro dissolution studies demonstrated that these ASDs improved the CEL dissolution rate by up to 8.2-fold compared to the crystalline form. Electrospraying presents a promising alternative to conventional methods like hot-melt extrusion (HME) and spraying drying (SD) for the production of ASDs, providing simplicity, high drug loading capability and long-term stability, thus catering to a variety of poorly water-soluble drugs. Graphical
研究领域:
药剂学
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药物递送系统
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DOI
PubMed
高影响因子
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