CRYSTAL GROWTH & DESIGN
·
2025
·
IF 3.4
Mengyang Cai,Pengpeng Yang,Jinqiu Fu,Guiyu Chen,Keke Zhang
In this study, 19F solid-state nuclear magnetic resonance (ss-NMR) was applied to explore the effect of pore surface chemical environment on the molecular assembly of celecoxib. Celecoxib, which is hydrophobic, was encapsulated in mesoporous silica modified with different functional groups via the melt-cooling method. The results indicated that mesoporous silica modified with the different functional groups could enhance and regulate the dissolution rate of celecoxib. The 19F NMR results demonstrated that celecoxib molecules prefer to assemble into liquid-like molecular layers, when confined in the pores modified with hydrophilic functional groups. In contrast, celecoxib molecules embedded in mesoporous silica materials modified with hydrophobic functional groups tend to aggregate in the pore center, forming central amorphous plugs. When different functional groups are modified within the pores, the varying interactions with celecoxib result in different proportions of molecular aggregation states within the pores. Besides that, the dissolution performance of confined celecoxib molecules was determined by the molecular aggregation in the pores. This work uncovers the relationship between surface chemistry and molecular aggregation, which is fundamental to designing porous materials for drug release.
研究领域:
药剂学
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材料科学
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物理化学
·
核磁共振（NMR）光谱学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qiao Qiao,Jie Li,Chunying Tao,Meiyang Yang,Weijun Chen,Lipeng Qiu,Huiming Tu
Studies have shown that inflammation is closely linked to the cancer development, and the patients with inflammatory bowel disease (IBD) have a higher risk of colon cancer. Celecoxib (CXB) and camptothecin (CPT) showed potential treatment for IBD and colon cancers, respectively. However, their applications are limited by synchronous delivery, water insolubility, and off-target side effects. Herein, a glutathione (GSH) responsive chondroitin sulfate A (CSA)-SS-CXB micelle loaded with CPT (CSA-SS-CXB@CPT) was prepared as a targeted system to treat colon cancer by anti-inflammatory and antitumor synergistic effect. Specifically, CSA had tumor tumor-targeting effect due to colon cancer lesion-high expression of CD44 receptors. In vitro results verified that CSA-SS-CXB@CPT selectively internalized into colon cancer HT-29 cells and had strong reactive oxygen species (ROS) elimination ability. The CSA-SS-CXB@CPT could rapidly release CXB and CPT in the tumor microenvironment for playing an anti-tumor role. In vivo experiments illustrated that CSA-SS-CXB@CPT significantly targeted tumor tissues and suppressed tumor growth without producing serious side effects in tumor-bearing nude mice. Therefore, this work provides an opportunity for targeted co-delivery of anti-inflammatory and chemotherapy drugs to treat colon cancer.
研究领域:
药学
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肿瘤学
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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
RUSSIAN JOURNAL OF GENERAL CHEMISTRY
·
2025
·Vol. 95
·期 9
·2445-2456
·
IF 0.8
Zhu Liqing,Wang Yimei,Liu Lang,Wei Yuan,De Minghao,Yu Hengli,Li Jianghai,Fu Xue
Celecoxib (CXB) is a non-steroidal anti-inflammatory drug, but its low aqueous solubility and bioavailability limit its clinical application. This study employed ternary solid dispersion technology (using PVP K30/sodium cholate as carriers) combined with rotary evaporation to prepare CXB solid dispersions for enhancing dissolution performance. Results demonstrated that the addition of PVP K30 and sodium cholate significantly improved the solubility of CXB, with the drug-polymer-surfactant ratio of 1 : 1 : 1.13 exhibiting maximum solubility and dissolution rate. The novel ternary solid dispersion achieved approximately 4.63-fold enhancement in solubility and 14.48-fold acceleration in dissolution rate (within 120 min). X-Ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) analyses confirmed the amorphous state dispersion of CXB and hydrogen bonding interactions with carriers. differential scanning calorimetry (DSC) revealed an elevated glass transition temperature ( T g ), indicating enhanced system stability. Contact angle experiments demonstrated significantly improved drug wettability by the carriers. In addition, after being stored at room temperature for three months, the stability of the CXB ternary solid dispersion is relatively good. This research provides a novel strategy for developing high-efficiency CXB formulations.
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2026
·
IF 4.3
Zhiling Chen,Huiling Zhou,Jie Song,Ben Xu,Can Wang,Fengchun He,Guisen Zhang,Tao Zhuang
Because the monotherapy of currently available pain killers often shows serious adverse effects or limited efficacy for treating neuropathic pain, multimodal analgesia has been highly recommended to gain improved antinociceptive effects and reduce dose-dependent side effects. Drug-drug co-amorphous systems emerge as a useful strategy for ameliorating the physicochemical properties of drug substances and achieving clinical benefits compared with individual components. New drug-drug co-amorphous products IMI-CEL at different ratios were prepared from imipramine hydrochloride (IMI) and a poorly water-soluble anti-inflammatory drug–celecoxib (CEL) by melt-quenching method, which were characterized by XRPD, DSC and IR. Co-amorphous product IMI-CEL (1:1) displayed notable improvement in the solubility (64.4 times) and dissolution rate (3.1 times) than crystalline CEL in pH 6.8 buffer, and IMI-CEL exhibited good physical stability under long-term storage conditions. Isobolographic analysis demonstrated that IMI-CEL (1:1) showed synergistic analgesic effects in paclitaxel-induced neuropathic pain in mice. Moreover, the oral bioavailability of 1:1 IMI-CEL was improved 1.396 times in rats when compared to the single drug. Above results suggested the potential of IMI-CEL to produce synergistic analgesic effects through developing drug-drug co-amorphous systems.
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DOI
PubMed
高影响因子
ChemMedChem
·
2023
·Vol. 18
·期 23
·e202300468
·
IF 3.4
Jingjie Fang,Ziyi Shang,Kumaravel Kaliaperumal,Zhiran Ju,Fen-Er Chen
Graphical This study presents a design strategy, synthesis, and evaluation of balanced COX inhibitors derived from natural anti-inflammatory ascidian metabolites and celecoxib, highlighting their potential therapeutic value in the context of inflammation. The serious adverse effects caused by non-selective and selective cyclooxygenase-2 (COX-2) inhibitors remain significant concerns for current anti-inflammatory drugs. In this study, we present the design and synthesis of a novel series of celecoxib analogs incorporating a hydrazone linker, which were subjected to in silico analysis to compare their binding poses with those of clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) against COX-1 and COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX enzymes, and compound 6 m , exhibiting potent balanced inhibition, was selected for subsequent in vitro anti-inflammatory assays. Treatment with 6 m effectively suppressed the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, resulting in reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), IL-1β, as well as decreased production of prostaglandin E 2 (PGE 2 ), nitric oxide (NO), and reactive oxygen species (ROS). However, 6 m has no effect on the MAPK signaling pathway. Therefore, due to its potent in vitro anti-inflammatory activity coupled with lack of cytotoxicity, 6 m represents a promising candidate for further development as a new lead compound targeting inflammation.
研究领域:
药理学
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药物化学
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炎症研究
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药物设计
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DOI
PubMed
高影响因子
RUSSIAN JOURNAL OF GENERAL CHEMISTRY
·
2024
·Vol. 94
·期 1
·170-183
·
IF 0.9
Li T.,Fu X.,Wang Y.,Ouyang F.,Liu L.,Wen M.,Zha G.,Zhu L.
Abstract Celecoxib (CXB) is a nonsteroidal anti-inflammatory drug (NSAID). However, the application of CXB has been compromised by its poor aqueous solubility and low oral bioavailability. We developed a series of ternary solid dispersions (SDs) of CXB to increase its solubility. In this study, the polymers were screened to determine that they have the potential to increase the solubility of CXB in the solution. A hydrophilic polymer-hydroxypropyl methylcellulose (HPMC) and a surfactant Tween80 were employed as matrix respectively in the optimized formulations. Experimental data revealed that CXB was molecularly distributed within all dispersions in amorphous form by using Differential Scanning Calorimetry (DSC), Polarizing Light Microscopy (PLM), and X-ray powder diffraction (XRD). Fourier Transform Infrared Spectroscopy (FTIR) results showed that the characteristic peaks of CXB have shifted. Compared with pure CXB, the addition of excipients can reduce the contact angle, and improve the solubility of CXB. Ternary SDs were dissolved in PBS (pH 6.8) and formed drug-carrying nanoparticles. In vitro dissolution results indicated that the dissolution amount of HPMC-CXB 5 : 1 SD (32.08±1.56% for 120 min) was higher than pure CXB (3.09±0.29%). In particular, the greatest dissolution enhancement was obtained from the test of which the result was HPMC/Tween80-CXB 3 : 2 : 1 SD (44.12±2.01% for 120 min). This study showed that ternary SDs could be a promising strategy for improving CXB dissolution.
研究领域:
药剂学
·
药物化学
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DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2022
·
IF 2.712
Jialiang Lin,Junchao Huang,Jiang Wu,Bo Tang,Congbin Li,Haijun Xiao
Traumatic heterotopic ossification (THO) is a serious and common clinical post-traumatic complication for which there is no effective and safe drug treatment. Routine administration of nonsteroidal anti-inflammatory drugs (NSAIDs) after injury is extensively used approach for THO. However, serious adverse events can occur in the event of an overdose of NSAIDs. In our study, we have developed a poly(lactic acid-co-glycolic acid) (PLGA) microsphere by emulsifying solvent volatilization for the prolonged slow delivery of celecoxib (CLX). Three groups of celecoxib-poly(lactic acid-co-glycolic acid) microspheres (CLX–PLGA MPs) were prepared with particle sizes of 3.75±1.28 μm, 49.56±17.15 μm, and 94.98±42.53 μm. Meanwhile, related parameters of microspheres in each group were studied: drug loading (DL), encapsulation rate (EE), and slow-release behavior. The DL and EE of the 3 CLX–PLGA MPs did not vary significantly, and subsequently, we selected the second drug loading microspheres with a retardation period of about 70 days for subsequent experiments. Moreover, cellular and animal experiments suggest that the microspheres are biocompatible and can be safely applied to localized trauma tissue. Finally, it is demonstrated that CLX–PLGA MPs have an effect on inhibiting the osteogenic differentiation of bone marrow mesenchymal stem cells and have the potential to inhibit ectopic bone formation of the THO model in Sprague-Dawley rat. Therefore, this study suggests that CLX–PLGA MPs are expected to be applied topically in the early post-traumatic period to prevent the development of THO.
研究领域:
药理学
·
生物医学工程
·
骨科
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 5.9
Zi-Jie Song,Xiao-Fei Wu,Zhi-Ya Zhou,Jing-Jing Zhang,Yan-Yan Pan,Xue Dong,Xuan Pang,Ya-Ping Xie,Juan Sun,Yu Zhang,Jie Qin
A library comprising twenty-four isosteric derivatives of celecoxib substituted with carboxylic acid (labeled as 5a - 5x ), was synthesized and characterized through 1 H NMR, 13 C NMR, HRMS, and elemental analysis. Molecular docking studies revealed that all compounds successfully docked into the binding pocket of COX-2, and the introduction of carboxyl group enhances the interaction between the derivatives and COX-2. The compounds were further evaluated for cell toxicity, and in vitro anti-inflammatory activity. Notably, compound 5l exhibited significant inhibition of both COX-2 and NO release in vitro in comparison to the standard compound, displaying the highest selectivity towards the COX-2 enzyme (SI = 295.9) in comparison to celecoxib (SI = 261.3). 5l also exhibited the most potent anti-inflammatory activity and safety (ulcer index = 5.2) in vivo comparable to celecoxib at the same concentration. Through the molecular modeling and dynamics analysis, it was observed that compound 5l effectively stabilized within the active binding site of COX-2 through strong hydrogen bond interactions, and through the ADMET studies investigated the physiochemical properties and drug-likeliness behavior of compound 5l . In conclusion, compound 5l demonstrated to be a potential selective COX-2 anti-inflammatory candidate with reduced gastrointestinal risks.
研究领域:
药理学
·
药物化学
·
炎症研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Mengwei Wang,Olivia Aalling-Frederiksen,Anders Ø. Madsen,Kirsten M.Ø. Jensen,Mads R.V. Jørgensen,Junbo Gong,Thomas Rades,Inês C.B. Martins
The influence of different preparation methods on the physicochemical properties of amorphous solid forms have gained considerable attention, especially with recent publications on pharmaceutical poly a morphism. In the present study, we have investigated the possible occurrence of poly a morphism in the drug celecoxib (CEL) by investigating the thermal behavior, morphology, structure, molecular mobility and physical stability of amorphous CEL obtained by quench-cooling (QC), ball milling (BM) and spray drying (SD). Similar glass transition temperatures but different recrystallization behaviors were observed for CEL-QC, CEL-BM and CEL-SD using modulated differential scanning calorimetry analysis. A correlation between the different recrystallization behaviors of the three CEL amorphous forms and the respective distinct powder morphologies, was also found. Molecular dynamics simulations however, reveal that CEL presents similar molecular conformational distributions when subjected to QC and SD. Moreover, the obtained molecular conformational distributions of CEL are different from the ones found in its crystal structure and also from the ones found in the lowest-energy structure obtained by quantum mechanical calculations. The type and strength of CEL hydrogen bond interactions found in CEL-QC and CEL-SD systems are almost identical, though different from the ones presented in the crystal structure. Pair distribution function analyses and isothermal microcalorimetry show similar local structures and structural relaxation times, respectively, for CEL-QC, CEL-BM and CEL-SD. The present work shows that not only similar physicochemical properties (glass transition temperature, and structural relaxation time), but also similar molecular conformational distributions were observed for all prepared CEL amorphous systems. Hence, despite their different recrystallization behaviors, the three amorphous forms of CEL did not show any signs of poly a morphism.
研究领域:
药剂学
·
材料科学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 3
·730
·
IF 5.4
Kedi Chu,Yi Zhu,Geng Lu,Sa Huang,Chuangzan Yang,Juying Zheng,Junming Chen,Junfeng Ban,Huanhuan Jia,Zhufen Lu
This study presents a method for a one-step co-encapsulation of PLGA nanoparticles in hydrophilic nanofibers. The aim is to effectively deliver the drug to the lesion site and achieve a longer release time. The celecoxib nanofiber membrane (Cel-NPs-NFs) was prepared by emulsion solvent evaporation and electrospinning with celecoxib as a model drug. By this method, nanodroplets of celecoxib PLGA are entrapped within polymer nanofibers during an electrospinning process. Moreover, Cel-NPs-NFs exhibited good mechanical strength and hydrophilicity, with a cumulative release of 67.74% for seven days, and the cell uptake at 0.5 h was 2.7 times higher than that of pure nanoparticles. Furthermore, pathological sections of the joint exhibited an apparent therapeutic effect on rat OA, and the drug was delivered effectively. According to the results, this solid matrix containing nanodroplets or nanoparticles could use hydrophilic materials as carriers to prolong drug release time.Keywords:nanoparticle;nanofiber;drug delivery;osteoarthritis
研究领域:
药学
·
纳米技术
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Ruijie Chen,Xinlu Lin,Qian Wang,Xingsi An,Xinyu Zhao,Yujie Lin,Tuyue Sun,Chenyang Yan,Aimin Cai,Weilan Cao,Youting Zhang,Qing Yao,Longfa Kou
Ulcerative colitis (UC) is a chronic recurrent disease of the gastrointestinal tract. Though the exact etiology is still unknown, inflamed enterocytes, activated macrophages, and the crosstalk between them have been widely believed to play vital roles in the UC progression. Therefore, simultaneously modulating both injured intestinal epithelial cells and activated immune cells could effectively normalize the intestinal microenvironment by regulating cell-specific activities and breaking the vicious loop between them. Herein, we designed a PepT1 and CD44 dual-targeted celecoxib nanoparticle ( [email protected] ) that could selectively deliver celecoxib to both the inflamed enterocytes and the activated M1 macrophages for UC treatment. [email protected] exhibited excellent cell-specific targeting ability to both inflamed epitheliums and M1 macrophages. In vitro studies showed that [email protected] could exert an enhanced anti-inflammatory effect and improve the colonic inflammatory microenvironment via directly modulating Nrf2/HO-1 and NF-κB pathways in epithelial cells and promoting M1 to M2 macrophage polarization. In a DSS-induced mice model, [email protected] significantly attenuated bodyweight loss, reduced colon length shortening, lowered the disease activity index score and alleviated colon histological damage. In addition, [email protected] could also regulate the intestinal flora in UC mice toward a healthier state with improved species uniformity and abundance as well as restored species diversity. Notably, both in vivo and in vitro data proved that [email protected] had more robust therapeutic activity than both Cel solution and single targeted nanoparticle. This study provides a potential strategy for UC drug delivery and effective treatment.
研究领域:
药学
·
生物医学工程
·
免疫学
·
胃肠病学
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产品关联
DOI
高影响因子
Applied Materials Today
·
2023
·
IF 8.3
Mingming Song,Bin Zhu,Shuang Qiu,Jiameng Tian,Jianning Li,Daling Chen,Chang Liu
Melanoma is one of the most aggressive and deadly forms of skin cancer, and effective treatments need to be developed. The combination of chemoimmunotherapy has emerged as a promising strategy for treating cancer. However, this strategy still has several limitations, including the inability of more than two drugs to reach tumor tissue simultaneously and the risk of serious adverse effects. The use of nanodrug delivery systems is an effective method to successfully combine these therapies, as they reduce side effects and improve bioavailability. In this study, we developed IL4RPep-1-targeting peptide nanoparticles (IPP NPs) for the codelivery of afuresertib and celecoxib for melanoma treatment by taking advantage of the high drug loading capacity and favorable pharmacokinetic profile of the poly(lactide-co-glycolide) nanoparticle platform. IPP NPs efficiently target three different types of melanoma cells in vitro and significantly accumulate at the tumor site in vivo . In both ectopic and pulmonary metastatic melanoma models, targeted codelivery of afuresertib and celecoxib not only promotes melanoma cell apoptosis but also reprograms M2-type macrophages into M1-type macrophages, reconstructing the tumor immune microenvironment and activating the immune response against cancer cells. In addition, this highly coordinated precise delivery of the drug to tumor cells significantly reduces adverse reactions associated with the combination of afuresertib and celecoxib. In summary, IPP NPs exhibit an accurate pH response and ideal targeted drug delivery capabilities for combination chemotherapy and immunotherapy, offering therapeutic potential for this combination in melanoma.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫学
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DOI
高影响因子
危险品化学品经营许可证（带存储）