查找使用阿拉丁产品的科研文献

COX-2/PGE2 axis blockade with celecoxib enhances anti-PD-1 efficacy by activating natural killer cells for residual hepatocellular carcinoma after radiofrequency ablation

Lei Yu,Bai Yaowei,Bai Xiatong,Sun Bo,Zhu Licheng,Wu Wenlong,Su Yang,Zhang Hongsen,Wang Yingliang,Zheng Chuansheng

Background and aims Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but incomplete ablation and recurrence of residual tumors remain significant challenges, partly due to local inflammation and elevated COX-2 levels in the tumor microenvironment. This study aims to investigate the potential of combining celecoxib, a COX-2 inhibitor, with anti-PD-1 monoclonal antibody (αPD-1) to enhance anti-tumor efficacy and activate immune responses. Methods In vitro, ELISA was used to assess the effects of radiofrequency heat treatment and celecoxib on PGE 2 secretion by Hepa1-6 cells. Scanning electron microscopy, flow cytometry, and CCK-8 assays were employed to evaluate the function and cytotoxic activity of NK92 cells against Hepa1-6 cells. In vivo, orthotopic HCC mice were divided into five groups to evaluate tumor volume, pathology, and survival. The role of celecoxib in the COX-2/PGE 2 /NK cell axis and its impact on NK cell immune function were investigated. Results In vitro experiments showed that celecoxib reversed PGE 2 -mediated suppression of NK cell function and cytotoxic activity against HCC cells by inhibiting PGE 2 secretion. In vivo, orthotopic HCC mice treated with celecoxib and αPD-1 exhibited significantly reduced tumor volumes, attenuated the infiltration and activation of NK cells, and prolonged survival compared to control groups. The combination therapy also demonstrated a notable abscopal-like effect, inhibiting metastatic tumor growth and activating systemic immunity. Conclusions Taken together, these findings suggest that celecoxib combined with αPD-1 represents a promising strategy for treating residual HCC after RFA, with enhanced anti-tumor effects and good safety. Graphical abstract

Hyaluronic Acid-Modified Celecoxib-Loaded Nanostructured Lipid Carriers Combined with Dissolving Microneedles for Targeted Sustained-Release Therapy in Osteoarthritis

Junfeng Ban,Yichao Li,Yanhua Guo,Huashen He,Chuangzan Yang,Peining Li,Jiawei Liang,Shirui Li,Xueyuan Luo,Yu Li,Yi Xie,Xiangmei Liu,Xiaofang Li

Background Rapid local drug clearance and poor sustained retention pose challenges to the treatment of osteoarthritis. Therefore, a local delivery system that prolongs intra-articular drug retention and achieves efficient targeted delivery holds significant clinical promise.Methods Hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-Cxb-NLCs) were prepared and encapsulated in dissolving microneedles to form a composite delivery system (HA-Cxb-NLCs-DMNs). The system was characterised in terms of its physicochemical properties, in vitro drug release profiles, transdermal permeation behaviour, cellular compatibility, and uptake mechanisms. Subsequently, a sodium iodoacetate-induced rat osteoarthritis model was used to evaluate the therapeutic efficacy in vivo.Results HA-Cxb-NLCs-DMNs exhibit a uniform particle size (113.93 ± 1.66 nm) and a zeta potential of (−39.16 ± 3.00 mV). In vitro release persisted for 72 hours, with a cumulative permeation of 62.74 ± 1.40 μg·cm−2 and a skin retention of 3.20 ± 0.62 μg·cm−2. HA modification enhances cellular uptake of the nanocarriers via the CD44 receptor. Animal studies demonstrated that it reduces joint swelling, improves cartilage damage, and inhibits MMP-13 expression.Conclusion This study presents a promising microneedle-nanoparticle synergistic delivery strategy for the local targeted therapy of osteoarthritis.

Preliminary Study on Different Types of Solid Dispersion Excipients for Improving the Water Solubility and Physical Stability of Celecoxib

Bin Liu,Shiqiao Rui,Yupan Cai,Ruoru Qian,Shuaipeng Feng,Zhu Liu,Qinfu Zhao

The solubilization of poorly water-soluble drugs remains a critical challenge in pharmaceutical research. The formulation of solid dispersions employing mesoporous silica nanoparticles (MSN) constitutes a key strategy for enhancing the hydrophilicity and oral bioavailability of Biopharmaceutics Classification System (BCS) Class II drugs. Although several commercial mesoporous silica excipients have been approved for pharmaceutical use, there remains room for improvement regarding drug loading capacity, stability, and controllability of drug release.Methods:for this purpose, dendritic mesoporous silica nanoparticles (DMSN) with a radial dendritic structure and pH-responsive degradation properties were designed and synthesized using celecoxib (CEL) as the model drug, featuring a pore size of 21.51 nm. CEL was loaded onto DMSN and seven commercial solid dispersion excipients using the solvent evaporation method.Results:owing to its high surface area, pore volume, and radial structure, DMSN achieved 39.72% drug loading in an amorphous state, markedly improving wettability, dissolution, and physical stability. Accelerated stability tests showed that DMSN inhibited recrystallization, outperforming traditional solid dispersions. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of CEL-DMSN was 1.29-fold higher than that of commercial celecoxib capsules.Conclusions:in conclusion, these results confirmed the potential of DMSN in enhancing the stability, promoting oral absorption, and reducing gastrointestinal irritation of poorly soluble drugs.

Preparation and In Vitro/Vivo Evaluation of New Celecoxib Solid Dispersions with Co-Carrier Containing Aerosil and Poloxamer 188

Shi Xiangjun,Ding Zejie,Bao Jiayin,Wang Chao

Solid dispersions (SDs) containing co-carrier were developed to improve in vitro dissolution and in vivo pharmacokinetics of celecoxib (CXB). Various polymers, including PVP K30, PEG4000, PEG6000, Poloxamer 188, Eudragit E100 and colloidal SiO 2 , were studied in the preparation of CXB-containing SDs. Poloxamer 188 and Aerosil stood out in preliminary characterization. Further study was focused on the selection and characterization of optimum ratio of CXB and polymer in solid dispersions (CXB-Poloxamer 188-Aerosil, 1:5:1). Results exhibited remarkable enhancement of both the dissolution and bioavailability of CXB which retained an amorphous form in SD samples.

Derma roller® microneedles-mediated transdermal delivery of doxorubicin and celecoxib co-loaded liposomes for enhancing the anticancer effect

Kamel S. Ahmed,Xiaotian Shan,Jing Mao,Lipeng Qiu,Jinghua Chen

The topical delivery of chemotherapeutics is a promising approach for the management of skin disorders. However, diverse pharmaceutical strategies are essential to allow penetration of large quantities of drugs to tumor tissue. Herein, an attempt was made to investigate the use of Derma roller® microneedles in combination with doxorubicin HCl (DOX) and celecoxib (CEL) co-loaded liposomes as a potential therapeutic approach for the management of melanoma. DOX/CEL co-loaded liposomes/Gels were prepared and characterized. The results showed that microneedle pretreatment with liposomes gel increased DOX penetration into the skin approximately 2-fold compared with the passive delivery. Both CEL liposomes and DOX liposomes caused significant growth inhibition on B16 cells. Besides, DOX/CEL co-loaded liposome was found more cytotoxic than DOX/CEL solution and single drug loaded liposome. The transdermal delivery of DOX/CEL co-loaded liposome successfully inhibited subcutaneous melanoma in female BALB/nude mice, and the co-administration of DOX/CEL with liposomes was better and significantly enhanced the antitumor effect more than single-drug-loaded liposomes. Furthermore, Dermarollers treatment prior to gel application strongly improved the tumor inhibition rate. DOX/CEL co-loaded liposome delivery via microneedles is a promising strategy for skin tumor treatment with targeting inhibition efficiency and negligible side effects.

Liposome-based codelivery of celecoxib and doxorubicin hydrochloride as a synergistic dual-drug delivery system for enhancing the anticancer effect

Kamel S. Ahmed,Sun Changling,Xiaotian Shan,Jing Mao,Lipeng Qiu,Jinghua Chen

Celecoxib-Loaded “Nano-in-Nano” Hierarchical Delivery System: Structure-Driven Synergistic Optimization of Diffusion Efficiency and Mechanical Stability for Osteoarthritis Therapy

Chuangzan Yang,Huashen He,Yichao Li,Sa Huang,Yingneng Zhang,Weixin Xiao,Zhixuan Peng,Xueyuan Luo,Shuohan Jiang,Yu Li,Liran Cen,Huanhuan Jia,Ying Liu,Junfeng Ban

Purpose Osteoarthritis (OA) joints present abnormal mechanical environments that limit drug retention and therapeutic efficacy. Current intra-articular systems cannot provide both sustained anti-inflammatory delivery and mechanical support. A celecoxib (CXB)-loaded “Nano-in-Nano” Hierarchical Delivery System (NiN-HDS) was developed to simultaneously optimize drug release and joint reinforcement.Methods In this study, celecoxib-loaded PLGA nanoparticles (CXB-NPs) were prepared by emulsion solvent evaporation and incorporated into an electrospun nanofiber membrane combined with a genipin-crosslinked gelatin layer to form NiN-HDS. The system was characterized for particle size, zeta potential, porosity, hydrophilicity, swelling, degradation, mechanical properties, and in vitro CXB release. Therapeutic potential was evaluated in a rat OA model using histological and immunohistochemical analyses of cartilage and inflammatory markers.Results NiN-HDS maintained nanoparticle stability, with CXB-NPs showing an average particle size of 138.4 ± 4.3 nm and a zeta potential of –58.74 ± 16.58 mV. The system exhibited high porosity (87.16 ± 0.75%) and hydrophilicity (contact angle < 90°), achieved swelling equilibrium at 150 ± 10 min with a swelling ratio of 163.97 ± 9.76%, and degraded over 10 days with 88.53 ± 2.03% mass loss. Mechanical testing demonstrated high strength (Young’s modulus 17.24 ± 2.65 MPa, elongation at break 307.48 ± 32.01%. NiN-HDS provided sustained CXB release over 7 days, reaching 67.16% cumulative release. In vivo, it reduced cartilage damage and suppressed IL-1β and MMP-13 expression, while maintaining mechanical support and controlled drug delivery.Conclusion In conclusion, we successfully developed NiN-HDS. Our results show that NiN-HDS combines sustained drug delivery with mechanical support, improves cartilage preservation and reduces local inflammation in a rat OA model, indicating that it can serve as a promising strategy for intra-articular therapy of osteoarthritis.

Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to radiation-induced apoptosis through downregulation of the Akt/mTOR signaling pathway and COX-2 expression

Pan Zhang,Dan He,Erqun Song,Mingdong Jiang,Yang Song

The current study aimed to identify the radiosensitizing effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in combination with radiotherapy in non-small-cell lung cancer (NSCLC) cells. The combination of celecoxib potentiated radiation-induced apoptosis; however, no changes in cell cycle distribution and number of phosphorylated histone H2AX foci were detected, indicating a DNA damage-independent mechanism. In an in vivo mouse model, the tumor size was significantly decreased in the group combining celecoxib with radiation compared with the radiation only group. Phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR), as well as expression of COX-2 were significantly downregulated in cells treated with the combination of celecoxib and radiation compared with the radiation only group. The result indicated that celecoxib exhibits radiosensitizing effects through COX-2 and Akt/mTOR-dependent mechanisms. Induction the Akt/mTOR signaling pathway promotes radioresistance in various cancers, including NSCLC. Therefore, the current study suggested the therapeutic potential of combination therapy of celecoxib and radiation in the prevention of radioresistance.

A pH-responsive injectable hydrogel that modulates the inflammatory microenvironment for the treatment of osteoarthritis

Dong-Wei Shao,Tong Xie,Ya-Tao Wang

Osteoarthritis (OA) is a widespread chronic degenerative joint disease, for which new treatment strategies are urgently needed. In this study, we developed an injectable, pH-responsive hydrogel (HA-TA-CS) aimed at improving joint drug delivery by enhancing retention within the joint cavity, while exhibiting excellent biocompatibility. The hydrogel was loaded with celecoxib for localized, in situ release (HA-TA-CS@Cel). OA is characterized by elevated levels of reactive oxygen species (ROS), which promote oxidative stress, inflammatory cytokine production, and further exacerbate the inflammatory response. HA-TA-CS@Cel effectively mitigates inflammation by scavenging excess ROS through the sustained release of TA and celecoxib. Our results demonstrate that HA-TA-CS@Cel significantly alleviates OA progression. In a mouse OA model, the system reduced pro-inflammatory factors and alleviated disease severity. Furthermore, HA-TA-CS@Cel promoted the polarization of macrophages from the M1 to the M2 phenotype, suggesting its ability to modulate the immune microenvironment and thereby attenuate joint inflammation and slow OA progression. These findings indicate that the injectable HA-TA-CS@Cel hydrogel system holds great promise for treating OA through enhanced cartilage protection and macrophage polarization, with potential applications in other inflammatory diseases.

Isopsoralen alleviates osteoarthritis by modulating the MAPK/NF-κB signaling pathway and regulating the structure of gut microbiota

Aoyu Zhang,Shuying Li,Jie Qiao,Chuanqi Zhong,Zhiwen Zhang,Xiguang Ye,Jun Jin,Shiyan Shang,Song Wu,Qing Zhang,Gongxu Yang

Ethnopharmacological relevance The therapeutic effect of Psoralea corylifolia L. on knee joint pain was recorded as early as the Ming Dynasty in the Compendium of Materia Medica, which notes its actions of tonifying the kidney, strengthening tendons, and bones. Isopsoralen (ISO), derived from the Psoralea corylifolia L., has shown efficacy in improving osteoarthritis (OA) in both traditional use and our previous screening, demonstrating effects in alleviating joint inflammation and protecting cartilage. Aim of the study OA is a common disabling disease. Its progression connects local joint pathology to systemic metabolic and inflammatory states, extending to gut microbiota and metabolites. This study examines the therapeutic mechanism of isopsoralen against OA using a DMM-induced model. Materials and methods ISO's targets were predicted by network pharmacology approaches. Therapeutic effects were evaluated through behavioral tests, micro-CT, histology, Western blot, and PCR, while safety was assessed via liver/kidney staining. 16S rDNA sequencing and targeted metabolomics were employed to analyze gut microbiota structure and short-chain fatty acids (SCFAs). Pseudo germ-free mice and fecal microbiota transplantation (FMT) were used to validate the role of gut microbiota. Results Network pharmacology indicated ISO's multi-target action against OA. ISO downregulated the MAPK/NF-κB pathway, attenuated subchondral bone abnormalities, and alleviated joint degeneration in DMM mice. It also modulated gut microbiota composition and SCFA levels. FMT confirmed the essential role of gut microbiota in ISO's efficacy. Furthermore, no hepatorenal toxicity was observed. Conclusion ISO alleviates OA by modulating gut microbiota/SCFAs and inhibiting the MAPK/NF-κB pathway, thereby reducing inflammation and improving bone abnormalities, without hepatorenal toxicity.

Friction-Adaptive Hydrogel Coating for Mechanical-Immune Synergy in Ligament-to-Bone Integration

Shuang Wang,Tianwu Chen,Yong Li,Lei Zhang,Jing Wang,Changsheng Liu

The long-term success of anterior cruciate ligament (ACL) reconstruction depends on the stable integration between artificial grafts and host bone. Despite their favourable mechanical strength, polyethylene terephthalate (PET) artificial ligaments often suffer from micromotion-induced fibrosis and persistent foreign body reactions (FBR), which together hinder osteointegration. Here, we develop a dual-network hydrogel coating with time-staged local immunomodulatory capability, enabling functional “mechano-immune” synergy at the graft-bone interface. Catechol-functionalized hyaluronic acid (HAMA-DOP) forms strong adhesive interactions with PET through π-π stacking, hydrogen bonding, and reversible covalent bonds. Subsequent oxidative crosslinking into a dense quinone-based secondary network enhances shear resistance and fatigue durability, while supporting self-healing. Pluronic F127 diacrylate (PF127-DA) introduces a thermoresponsive structure allowing the hydrogel to transition from injectable fluid at 4 °C to a stable gel at 37 °C, enabling localized and phase-specific release of celecoxib (CXB). This facilitates early suppression of inflammation and sustained promotion of regeneration. In vivo studies reveal a dose-dependent regulatory effect of CXB, where low-dose delivery promotes M2 macrophage polarization, H-type vessel formation, and bone bridging, while high doses impair immune homeostasis and osteointegration. This work establishes a robust, biologically responsive interface strategy, advancing the design of innovative coatings for enhanced outcomes in artificial ligament integration.

An Injectable Metal‐Drug Supramolecular Condensate Enables Radiosensitization and Systemic Antitumor Immunity for Post‐Surgical Osteosarcoma Therapy

Tianhua Xiao,Zunlei Gong,Chuke Chen,Hui Yu,Yu Cai,Can Liu,Hongkai Huang,Ying Li,Jinyuan Guan,Le Wang,Chengyun Ning,Guoxin Tan,Lei Zhou

Radiotherapy (RT) is widely used as an adjuvant treatment after surgical resection for osteosarcoma, but its efficacy is often limited by insufficient radiosensitization and an immunosuppressive tumor microenvironment that restricts systemic antitumor immunity and promotes recurrence and metastasis. Here we report an injectable metal‐drug supramolecular condensate formed from hafnium ions and alendronate (Hf‐ALN) and loaded with the COX‐2 inhibitor celecoxib (CXB) for synergistic radioimmunotherapy of postoperative osteosarcoma. The condensate forms through coordination‐driven liquid‐liquid phase separation between Hf 4+ ions and alendronate, enabling local retention within postoperative bone defects and sustained therapeutic release. Upon X‐ray irradiation, the Hf component amplifies radiation energy deposition and reactive oxygen species generation, thereby enhancing radiation‐induced DNA damage and immunogenic cell death. Meanwhile, the acidic tumor microenvironment triggers responsive release of CXB and ALN; CXB inhibits the COX‐2/PGE 2 immunosuppressive pathway, while ALN promotes macrophage repolarization toward the M1 phenotype, collectively remodeling the tumor immune microenvironment. This strategy enhances dendritic cell maturation, activates cytotoxic CD8 + T cells, and reduces regulatory T‐cell infiltration. In orthotopic osteosarcoma models, CXB@Hf‐ALN combined with RT suppresses tumor recurrence, preserves bone integrity, inhibits pulmonary metastasis, and prolongs survival with minimal systemic toxicity, offering a promising strategy to improve postsurgical RT outcomes in osteosarcoma. This work designed an injectable metal‐drug supramolecular condensate formed from hafnium ions and alendronate (Hf‐ALN) and loaded with the COX‐2 inhibitor celecoxib (CXB) for synergistic radioimmunotherapy of postoperative osteosarcoma. Mechanistically, upon X‐ray irradiation, Hf enhances radiation energy deposition, ROS generation, and DNA damage, while CXB blocks COX‐2/PGE 2 and ALN repolarizes M1 macrophages, remodeling immune microenvironment to inhibit recurrence/metastasis and preserve bone integrity.