COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Wei Gu,Qinfu Zhao,Ye He,Shengyu Wang,Yuanqi Yang,Yian Li,Shuaipeng Feng,Siling Wang
Mesoporous carriers have gained significant attention for enhancing the solubility and bioavailability of Biopharmaceutics Classification System (BCS) Class II drugs. However, the contribution of mesoporous carriers with varying morphologies to the physical stability of these drugs is not well-defined. In this work, mesoporous carbon nanoparticles (MCN) and hollow carbon mesoporous nanoparticles (HMC) were prepared, while the weakly acidic Indomethacin (IMC) and alkaline Celecoxib (CXB) were incorporated into these carriers in the amorphous state by the solvent evaporation method. Notably, HMC demonstrated superior drug loading efficiencies (approximately 43 %) for both IMC and CXB owning to its hollow structure. The mesoporous drug loading systems significantly enhanced dissolution rates in comparison with both self-made amorphous drugs and raw drugs. Furthermore, under accelerated and long-term storage conditions, the mesoporous carriers effectively prevented drugs loaded from crystallization, maintaining constant dissolution profiles for over 12 months. Intriguingly, CXB exhibited a slower rate of crystallization after loading into the mesoporous carriers, likely due to the formation of hydrogen bonds between the carbonaceous carrier material and the amino groups of CXB. Compared with loaded drugs, the self-made amorphous drugs exhibited a crystallinity increase beyond 60 % within the initial month. Collectively, these findings highlighted the potential of mesoporous carbon carriers to elevate the dissolution behaviors of BCS Class II drugs while preserving the physical stability of the loaded amorphous drugs.
研究领域:
药剂学
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材料科学
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PubMed
高影响因子
Future Medicinal Chemistry
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2021
·Vol. 13
·期 11
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IF 3.808
Baowei Yang,Yicheng Mei,Qianhui Li,Mengyuan Zhang,Huiling Tang,Tong Liu,Feng Feng,Qiyun Fu,Yuzhang Jiang,Qizhuang Ye
There is an urgent need for new antibiotics and alternative strategies to combat bacterial pathogens. Molecular docking, antibacterial evaluation in vitro and in vivo, cytotoxicity assessment and enzyme inhibition analyses were performed. Compound 12 exhibited antimicrobial activity against Staphylococcus aureus (MIC: 4 μg/ml), various clinically isolated strains of MRSA (MIC: 4–16 μg/ml) and Acinetobacter baumannii (MIC: 4 μg/ml) when combined with subinhibitory concentrations of colistin B. Compound 12 (20 mg/kg) yielded mild improvement in survival of methicillin-resistant Staphylococcus aureus (MRSA)-infected mice. Additionally, enzyme inhibition tests showed that compound 12 exhibited inhibitory effects against S. aureus dihydrofolate reductase (105.1 μg/ml) and DNA gyrase (122.8 μg/ml). Compound 12 is a promising antibacterial candidate for further development.Graphical abstractCelecoxib analogue 12 possesses considerable antibacterial activity in vivo and in vitro and is relatively safe, making it a promising lead for further optimization as an antibacterial therapeutic agent.
研究领域:
药理学
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微生物学
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医学
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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,Yang Fujia,Wang Fan,Qu YaMeng,Hu Liandong
Osteoarthritis is associated with a weakly acidic intra-articular microenvironment, which provides an intrinsic trigger for pH-responsive drug delivery systems to achieve site-specific and controlled drug release, thereby enhancing therapeutic efficacy. In this study, celecoxib (CXB)-loaded microspheres (CM-10) for intra-articular injection were fabricated using a microfluidic technique with poly(lactic-co-glycolic acid) (PLGA)/CaCO₃ as the carrier. The microspheres were systematically characterized in terms of morphology, encapsulation efficiency, and physicochemical properties. Their pH-responsive drug release and degradation behaviors were evaluated under different in vitro conditions, and the degradation behavior following intra-articular injection was further investigated. In addition, the pharmacodynamic effects of CM-10 were assessed in an osteoarthritis model. The results demonstrated that CM-10 exhibited pronounced pH-responsive release, with accelerated drug release under acidic conditions and sustained degradation following intra-articular administration. Furthermore, CM-10 effectively promoted articular cartilage repair and improved therapeutic outcomes. These findings indicate that CM-10 has promising potential as a pH-responsive intra-articular drug delivery system for osteoarthritis therapy.
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高影响因子
JOURNAL OF MICROENCAPSULATION
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2021
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IF 3.142
Muhammad Asim Farooq,Amna Jabeen,Bo Wang
Aim Current study aimed to improve the solubility and release profile of the celecoxib for cancer application. However, the low water solubility of celecoxib limited its application for cancer chemotherapy. Hence, new drug delivery-based approaches are compulsory for the efficient delivery of hydrophobic celecoxib for chemotherapy.Methods The celecoxib-loaded nanocrystals were prepared by anti-solvent precipitation-ultrasonication technique, and the formulation was optimised through various process parameters.Results The optimised formulation had an average particle diameter of 171.09 ± 6.23 nm, with a PDI of 0.123 ± 0.009 and high ZP −27.3 ± 0.2 mV. The optimised formulation was stable, had higher entrapment efficiency 97.26 ± 1.12%. The conformational changes in the denatured protein solution were detected through fluorescence spectroscopy. The transmission electron microscopy investigation showed rod-shaped nanocrystals morphology, and no chemical interactions were observed in optimised formulation through FTIR. The DSC and PXRD analysis exhibited an amorphous state of the freeze-dried formulation drug. Also, optimised nanocrystals enhance drug solubility around 26.01-fold, 15.51-fold and 19.08-fold in purified water, pH 6.8 and pH 7.4, and accomplish sustained drug delivery, respectively.Conclusion It can be concluded that biopolymer-coated celecoxib nanocrystals might be potential drug delivery of hydrophobic molecules for cancer therapy.
研究领域:
药剂学
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肿瘤学
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PubMed
高影响因子
PHARMACEUTICAL RESEARCH
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2022
·Vol. 40
·期 2
·567-577
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IF 4.58
Chen An,Cai Peishan,Luo Minqian,Guo Minshan,Cai Ting
Purpose The fixed-dose combination drug products have been increasingly used to treat some complex diseases. A cocrystal containing two therapeutic components, named as a drug-drug cocrystal, is an ideal solid form to formulate as a fixed-dose combination product. The aim of the study is to prepare celecoxib-carbamazepine (CEL-CBZ) cocrystals by melt crystallization to achieve the synchronized release of drugs. Method The crystal structure of the CEL-CBZ cocrystal was determined from the cocrystals harvested from melt by single crystal X-ray diffraction. The binary phase diagram and crystal growth kinetics of the CEL-CBZ cocrystal from melt were studied to optimize the process parameters of hot-melt extrusion for manufacturing large-scale cocrystals. The intrinsic dissolution rate studies were conducted to compare the dissolution profiles of drugs in the cocrystal and their individual forms. Result The CEL-CBZ cocrystal crystallized in the triclinic space group with one CEL and one CBZ molecule in the asymmetric unit. The crystallization of CEL-CBZ cocrystals were observed both in the supercooled liquid and glassy state. The formation of drug-drug cocrystals significantly alter the intrinsic dissolution rates of the parent drugs to favor the synchronized release. Conclusion Melt crystallization is an alternative, efficient and eco-friendly approach for preparing drug-drug cocrystals on a large scale. The synchronized drug release by drug-drug cocrystals can be used to modulate the release profiles of parent drugs in the fixed-dose combination products.
研究领域:
药学
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药物化学
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结晶工程
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PubMed
高影响因子
Nanomedicine
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2024
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IF 4.7
Geng Lu,Chuangzan Yang,Kedi Chu,Yi Zhu,Sa Huang,Juying Zheng,Huanhuan Jia,Junfeng Ban,Xiaofang Li
Background: Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. Materials & methods: This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. Results: Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. Conclusion: These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression.Graphical abstract
研究领域:
药学
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材料科学
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生物医学工程
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骨科
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PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2022
·Vol. 26
·期 14
·3995-4006
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IF 5.295
Cong Zhang,Yuzhen Lu,Yingying Song,Liang Chen,Junjie Hu,Yan Meng,Xin Chen,Shan Li,Guohua Zheng,Zhenpeng Qiu
Mounting evidence indicates that hepatic de novo lipogenesis is a common abnormality in non-alcoholic fatty liver disease (NAFLD) patients. We investigated whether a selective COX-2 inhibitor, celecoxib, alleviates hepatic steatosis by targeting an Akt-driven lipogenic pathway. We estimated the efficacy of celecoxib in a novel Akt-driven NAFLD mouse model established via hydrodynamic transfection of activated forms of AKT and in fructose-fed NAFLD mice that exhibited increased insulin-independent hepatic lipogenesis. AKT-transfected and insulin-stimulated human hepatoma cells were used for the in vitro experiments. Haematoxylin and eosin staining, immunohistochemistry and immunoblotting were performed for mechanistic studies. The results revealed that celecoxib ameliorated hepatic steatosis in the AKT-triggered NAFLD mice. Mechanistically, celecoxib effectively suppressed AKT/mTORC1 signalling and its downstream lipogenic cascade in the Akt-driven NAFLD mice and in vitro. Furthermore, celecoxib had limited efficacy in alleviating hepatic lipid accumulation and showed no influence on lipogenic proteins associated with hepatic lipogenesis in fructose-administered mice. This study suggests that celecoxib may be favourable for the treatment of NAFLD, especially in the subset with Akt-triggered hepatic lipogenesis.
研究领域:
药理学
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肝病学
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代谢性疾病
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PubMed
高影响因子
Pharmaceutics
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2025
·Vol. 17
·期 4
·511
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IF 5.5
Qiao Qiao,Xian Wan,Jie Li,Weijun Chen,Enxuan Li,Lipeng Qiu,Huiming Tu
Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application.Methods: We reported a novel chondroitin sulfate A–Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated.Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of −22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice’s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine.Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug.
研究领域:
药剂学
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炎症性肠病治疗
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生物材料
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Minqian Luo,An Chen,Shiyu Shan,Minshan Guo,Ting Cai
Coamorphous drug delivery systems have emerged as a promising formulation strategy to enhance the solubility, oral bioavailability, and physical stability of poorly water-soluble drugs. The molar ratio of components in coamorphous systems plays a critical role in determining their physical stability. In this study, we investigated the crystallization behavior of coamorphous celecoxib–carbamazepine (CEL–CBZ) systems at different molar ratios. The growth rates of CEL crystals, CBZ crystals, and CEL–CBZ cocrystals were observed to exhibit distinct dependencies on the molar ratio of coamorphous systems, primarily due to their unique thermodynamic driving forces, despite sharing the same kinetic factor. The influence of the molar ratio on the crystallization of coamorphous systems arises from the interplay between its effects on molecular mobility and thermodynamic driving forces, leading to either cooperative or competing effects. Both the crystal growth and crystallization tendency results reveal that thermodynamics plays a more dominant role than kinetics in the crystallization of coamorphous CEL–CBZ systems across various molar ratios. This study provides fundamental insights into the mechanism by which the molar ratio influences the crystallization of coamorphous systems, highlighting the complex crystallization behavior of multicomponent amorphous systems as an interplay between kinetics and thermodynamics.
研究领域:
药剂学
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药物化学
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2026
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IF 5
Jingjing Liu,Ling Yin,Wenjing Yang,Yanghua Qin,Chengyun Yan,Bingli Jiang,Yueyi Deng
Celecoxib (Cel) has extremely poor aqueous solubility, low bioavailability, and unsatisfactory powder mechanical properties for its tablet formulation development. Three cocrystals of Cel with tartaric acid (Ta), cinnamic acid (Ca), and salicylamide (Sal) were prepared to improve these properties of Cel and characterized by PXRD, DSC and FTIR. The cocrystals underwent comprehensive in vitro characterization, encompassing equilibrium solubility, dissolution, and tabletability profiling, followed by in vivo pharmacokinetic evaluation to assess bioavailability and pharmacodynamic performance. The results demonstrated significant improvements in pharmaceutical properties by preparing the cocrystals of Cel. The equilibrium solubility of the Cel-Ca cocrystal was 3.4 times of that of Cel, and the maximum dissolution of the Cel-Sal cocrystal was about 2.7 times of that of Cel. The tensile strengths of the cocrystals were greater than the critical tensile strength of 1.7 MPa for the formation of tablets, and the three cocrystals could be used for direct tabletting. In vivo pharmacokinetic studies showed that the cocrystals shortened the peak concentration time of oral absorption of Cel and significantly enhanced the relative bioavailability.
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高影响因子
MATERIALS & DESIGN
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2024
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IF 7.6
Honglin Xiang,Chuan Zhang,Yongfu Xiong,Yong Wang,Chaoyu Pu,Jiangtao He,Lu Chen,Ke Jiang,Weikang Zhao,Hanfeng Yang,Fan Wang,Yuling Li
Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.
研究领域:
药理学
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生物医学工程
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骨科
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药物递送系统
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Mingyue Yin,Xinyi Xiao,Yang Xiao,Jingyan Zhou,Shuxian Liu,Xue Jiang,Xiaomin Han,Tao Zhuang,Yin Chen
Chemotherapy-induced peripheral neuropathy (CIPN) represents a common dose-limiting adverse effect of chemotherapeutic drugs, affecting 25-90% of cancer patients. However, currently available medications often show limited efficacy for CIPN, which necessitates the development of novel analgesics. An emerging perspective is that neuroinflammation represents one of the possible pathogeneses underlying CIPN. In our studies, isobolographic analysis revealed that co-administration of celecoxib with pregabalin or gabapentin produced antinociceptive effects for CIPN. Based on multimodal analgesia, two new co-drugs CEL-PRE and CEL-GBP were synthesized from celecoxib with pregabalin/gabapentin to achieve synergistic antinociceptive effects for CIPN. Both CEL-PRE and CEL-GBP showed more than 200 times higher water solubility than celecoxib. In vitro liver microsome assays showed that these co-drugs can be metabolized into two parent drugs within 30 min. CEL-PRE and CEL-GBP exhibited significant efficacy in paclitaxel-induced neuropathic pain models with ED 50 values of 4.27 mg/kg and 6.55 mg/kg, respectively. At equimolar doses, CEL-PRE and CEL-GBP demonstrated superior antinociceptive effects than single drugs for paclitaxel-induced neuropathy. Both of the two co-drugs can alleviate inflammation by inhibiting inflammatory mediators (IL-6, IL-1β, TNF-α, COX-2, and PGE 2 ) and suppress the expression of neuronal c-Fos, which were significantly elevated in CIPN. Additionally, CEL-PRE and CEL-GBP do not affect motor coordination in rotarod tests. Therefore, novel co-drugs CEL-PRE and CEL-GBP are promising candidates for treating CIPN.
研究领域:
药理学
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肿瘤学
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神经科学
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PubMed
高影响因子
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