Journal of Drug Targeting最新文献_第8页

Nose-to-brain delivery of transferrin-modified carmustine-loaded iron nanoparticles for enhanced glioblastoma treatment. 转铁蛋白修饰的负载卡莫司汀的铁纳米颗粒经鼻至脑递送用于增强胶质母细胞瘤治疗。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-28 DOI: 10.1080/1061186X.2025.2526713

Hong Wang, Qingguo Ren, Guojian Wu, Jun Kong, Xingxing Jin, Pingzhong Huang, Kun Yang

{"title":"Nose-to-brain delivery of transferrin-modified carmustine-loaded iron nanoparticles for enhanced glioblastoma treatment.","authors":"Hong Wang, Qingguo Ren, Guojian Wu, Jun Kong, Xingxing Jin, Pingzhong Huang, Kun Yang","doi":"10.1080/1061186X.2025.2526713","DOIUrl":"10.1080/1061186X.2025.2526713","url":null,"abstract":"Glioblastoma multiforme (GBM) treatment is hindered by the blood-brain barrier (BBB) and an immunosuppressive tumour microenvironment (TME) rich in M2 tumor-associated macrophages (TAMs). Carmustine (BCNU) efficacy is limited by systemic toxicity. To address this, we developed transferrin-modified, BCNU-loaded superparamagnetic iron oxide nanoparticles (Tf/BCNU-SPIONs) for nose-to-brain delivery. Optimized Tf/BCNU-SPIONs were monodisperse (41.92 ± 2.81 nm), with high BCNU encapsulation (>80%) and transferrin anchoring (∼98%). Cellular studies showed Tf/BCNU-SPIONs enhanced Gl261 cellular uptake 2.1-fold versus non-targeted nanoparticles, achieving 76.4 ± 6.29% apoptosis at 8 h. In orthotopic GBM mice, single-dose intranasal administration suppressed tumour growth by 84.6 ± 5.3% (p < 0.01 vs. saline) and extended maximum survival to >60 days (vs. 48 days for free BCNU), due to BBB bypass and transferrin targeting. Crucially, SPIONs reprogrammed TAMs in the TME, increasing M1 polarization to 41.8 ± 6.5% (vs. 6.5 ± 3.2% in controls, p < 0.01). Safety assessments showed minimal hepatorenal/hematologic toxicity (p > 0.05 vs. saline) at just 20% of the clinical BCNU dose. This work establishes a synergistic chemo-immunotherapeutic strategy that concurrently overcomes BBB limitations, reprograms the immunosuppressive TME, and mitigates systemic toxicity, demonstrating promising preclinical efficacy.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bipartite 5-fluorouracil and lepidine-based nanoemulsion gel: in vitro and dermatokinetic evaluation. 基于5-氟尿嘧啶和lepidin的纳米乳凝胶：体外和皮肤动力学评价。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-25 DOI: 10.1080/1061186X.2025.2533333

Zeba Usmani, Samreen Jahan, Zakiya Usmani, Abdul Ahad, Mohd Akhtar, Mohd Aqil, Mohd Mujeeb

{"title":"Bipartite 5-fluorouracil and lepidine-based nanoemulsion gel: in vitro and dermatokinetic evaluation.","authors":"Zeba Usmani, Samreen Jahan, Zakiya Usmani, Abdul Ahad, Mohd Akhtar, Mohd Aqil, Mohd Mujeeb","doi":"10.1080/1061186X.2025.2533333","DOIUrl":"10.1080/1061186X.2025.2533333","url":null,"abstract":"Skin cancer is the most prevalent malignancy, with rising incidence and morbidity, particularly among the white population. This study aims to develop a dual drug-loaded nanoemulsion (NE) gel incorporating 5-fluorouracil (5-FU) and lepidine (LPD) to enhance drug deposition in the stratum corneum and dermal layer for improved skin cancer therapy. Oil-in-water (o/w) NEs were prepared using peppermint oil, Tween 80 and PEG-400 via aqueous phase titration method and optimised through pseudo-ternary phase diagrams. The optimised dual drug-loaded NE showed particle size of 131.7 ± 3.21 nm, PDI of 0.21 ± 0.005 and zeta potential of -26.24 ± 1.532 mV. This NE was then dispersed into a 1% carbopol 934 gel for topical application. In vitro and ex vivo studies demonstrated significantly enhanced drug deposition and prolonged release (**p < .001) compared to a conventional gel. Furthermore, dermatokinetic and CLSM studies confirmed enhanced skin permeation and deeper drug distribution. Skin irritation studies indicated that the NE gel was safe and non-irritant. It is concluded that the developed 5-FU and LPD co-loaded NE gel enhances topical drug delivery against skin cancer by improving drug absorption and distribution between the epidermis and dermis in rodent skin model, which could represent promising strategy for the management of skin cancer.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":4.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy of intranasal delivery of VEGFR inhibitors to cervical lymph nodes for inhibiting tongue cancer metastasis in mice. 经鼻给药VEGFR抑制剂抑制小鼠颈淋巴结舌癌转移的疗效。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-23 DOI: 10.1080/1061186X.2025.2531424

Tomoyuki Furubayashi, Minori Kobayashi, Nao Hamada, Shuichi Kawashiri, Akiko Tanaka

{"title":"Efficacy of intranasal delivery of VEGFR inhibitors to cervical lymph nodes for inhibiting tongue cancer metastasis in mice.","authors":"Tomoyuki Furubayashi, Minori Kobayashi, Nao Hamada, Shuichi Kawashiri, Akiko Tanaka","doi":"10.1080/1061186X.2025.2531424","DOIUrl":"10.1080/1061186X.2025.2531424","url":null,"abstract":"Oral cancers frequently metastasise to adjacent cervical lymph nodes (CLNs), leading to systemic dissemination and poor prognosis. Intranasal (i.n.) drug delivery provides direct access to cervical lymphatics, enabling high local drug concentrations while minimising systemic exposure. This study evaluated the pharmacokinetics (PK) and anti-metastatic efficacy of two vascular endothelial growth factor receptor (VEGFR)-3 inhibitors - cediranib maleate (CDNB) and pazopanib hydrochloride (PPNB) - administered i.n. in a mouse model of tongue cancer. Pharmacokinetic analysis showed that i.n. delivery yielded significantly higher CLN concentrations of both drugs than intravenous administration, despite lower plasma levels. In tumour-bearing mice, i.n. CDNB markedly reduced the incidence of CLN metastasis (0.167) versus controls (0.875, p < .01) and was more effective than intraperitoneal CDNB (0.571) or i.n. PPNB (0.500). Although less potent, PPNB significantly reduced the number of metastatic CLNs (0.438, p < .05). CDNB exhibited superior and more consistent efficacy. The reduced effect of PPNB may reflect its lower dose - limited by solubility - and possible differences in target specificity. These findings highlight the potential of i.n. administration to deliver VEGFR-3 inhibitors to CLNs, suppress lymphangiogenesis and lymphatic metastasis, and reduce systemic toxicity. This approach may offer a non-invasive alternative to neck dissection in oral cancer.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning for genomic profiling and drug discovery in personalised lung cancer therapeutics. 机器学习在个体化肺癌治疗中的基因组分析和药物发现。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-22 DOI: 10.1080/1061186X.2025.2530656

Shaban Ahmad, Syed Naseer Ahmad Shah, Rafat Parveen, Khalid Raza

{"title":"Machine learning for genomic profiling and drug discovery in personalised lung cancer therapeutics.","authors":"Shaban Ahmad, Syed Naseer Ahmad Shah, Rafat Parveen, Khalid Raza","doi":"10.1080/1061186X.2025.2530656","DOIUrl":"10.1080/1061186X.2025.2530656","url":null,"abstract":"Lung cancer is a leading cause of cancer-related mortality, with approximately 2 million new cases and 1.8 million deaths annually, and studies suggest that by 2050, these numbers will reach 3.8 million cases and 3.2 million deaths. The high mortality rate highlights the urgent need for early diagnosis and rapid drug development. Genomic approaches provide insights into tumour biology, supporting personalised medicine. This study explores the role of machine learning (ML) in enhancing genomic analysis and drug discovery for lung cancer treatment. A comprehensive PubMed search was conducted to identify relevant publications from the last 10 years. Selected studies were critically reviewed to understand how ML algorithms are applied in lung cancer genomics and drug discovery. ML algorithms such as random forests, gradient boosting, support vector machines, autoencoders, CNNs, and RNNs are widely used for genomic pattern identification. Techniques like reinforcement learning, deep neural networks, GANs, and GNNs are employed for drug discovery. ML models have achieved over 95% accuracy in certain lung cancer applications. However, challenges remain, including data scarcity and model interpretability. ML significantly enhances lung cancer's genomic analysis and drug design; however, further optimisation and clinical validation are essential for effective real-world implementation.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-20"},"PeriodicalIF":4.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The enhanced surface permeability and retention effect of topically administrated nanoparticles. 局部给药纳米颗粒增强表面渗透性和滞留效果。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-07-22 DOI: 10.1080/1061186X.2025.2534184

Yiyang Chen, Zhenghong Liu, Bin Zheng, Chenkai Wang, Xintao Hua, Pu Zhang, Dahong Zhang

引用次数: 0

Development and characterization of Ag-NPs coated silk sutures: a novel approach to inhibit surgical site infections. Ag-NPs包覆丝线的开发和特性：一种抑制手术部位感染的新方法。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-21 DOI: 10.1080/1061186X.2025.2534176

Sunirmal Bhattacharjee, Debjani Sarkar, Richa Dayaramani, Sweet Naskar, Suraj Sharma, Shounak Sarkhel

{"title":"Development and characterization of Ag-NPs coated silk sutures: a novel approach to inhibit surgical site infections.","authors":"Sunirmal Bhattacharjee, Debjani Sarkar, Richa Dayaramani, Sweet Naskar, Suraj Sharma, Shounak Sarkhel","doi":"10.1080/1061186X.2025.2534176","DOIUrl":"10.1080/1061186X.2025.2534176","url":null,"abstract":"Sutures play an essential role in surgical operations, as they secure and stabilise the edges of wounds to facilitate healing. Nonetheless, microbes on sutures can heighten the likelihood of surgical site infections (SSI) because of pathogen colonisation. This research focused on addressing surgical site infections (SSI) by creating silver nanoparticles (Ag-NPs) through a modified nanoprecipitation technique and utilising them to coat antimicrobial sutures. The physiochemical characteristics of Ag-NPs were confirmed by morphology (through TEM) with a particle size of 26.23 ± 0.234 nm, a PDI of 0.383 ± 0.156, and a zeta potential range of 1.04 ± 0.0.98 mV. Drug content and release studies were conducted for Ag-NP-coated silk sutures. Scanning electron microscopy (SEM) was conducted to determine the coating of Ag-NP-coated silk sutures. Antimicrobial activity was studied using five microorganisms (E. coli, P. aeruginosa, E. faecalis, S. aureus, and T. asperellum) for Ag-NP-coated silk sutures. The cytotoxicity of the Ag-NP-coated silk sutures was investigated using HaCaT for 24 h, which exhibited good cell viability. Finally, this study evaluates the pharmacokinetics of Ag-NP-coated silk sutures in a rat model to determine the pharmacokinetic profile of Ag. Overall, the results indicate that Ag-NP-coated sutures can potentially be used as antimicrobials to diminish or inhibit SSI in postoperative or general surgery patients.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-13"},"PeriodicalIF":4.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel furo[2,3-d]pyrimidine-based chalcone derivative (MMK-1931) loaded chitosomes as a potential cancer therapy in an Ehrlich ascites tumour model. 一种新型的呋喃[2,3-d]嘧啶基查尔酮衍生物（MMK-1931）负载壳质体作为一种潜在的治疗埃利希腹水肿瘤模型的癌症方法。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-18 DOI: 10.1080/1061186X.2025.2530651

Walaa A El-Dakroury, Moataz B Zewail, Mai A Mansour, Osama A Mohammed, Ahmed S Doghish, Ahmed Senbel, Al-Aliaa M Sallam, Mostafa I Gebril, Khaled A M Abouzid, Mina Noshy, Yousra A Nomier, Mamdouh A Oraby

{"title":"A novel furo[2,3-d]pyrimidine-based chalcone derivative (MMK-1931) loaded chitosomes as a potential cancer therapy in an Ehrlich ascites tumour model.","authors":"Walaa A El-Dakroury, Moataz B Zewail, Mai A Mansour, Osama A Mohammed, Ahmed S Doghish, Ahmed Senbel, Al-Aliaa M Sallam, Mostafa I Gebril, Khaled A M Abouzid, Mina Noshy, Yousra A Nomier, Mamdouh A Oraby","doi":"10.1080/1061186X.2025.2530651","DOIUrl":"10.1080/1061186X.2025.2530651","url":null,"abstract":"The pursuit of effective, non-invasive cancer therapies has propelled the development of oral delivery systems capable of overcoming the limitations of conventional chemotherapy. A novel furo[2,3-d]pyrimidine-based chalcone derivative, MMK-1931, was successfully encapsulated into chitosan-coated liposomes (chitosomes) to create an oral anticancer nanomedicine. Both MMK-1931-loaded liposomes and chitosomes were formulated, producing spherical nanoparticles (NPs) with a nanometric size range and high entrapment efficiency. Optimisation studies were conducted to select the most effective formulation. Structural characterisation using FTIR and differential scanning calorimetry (DSC) confirmed drug encapsulation and formulation integrity. In vivo evaluation in an Ehrlich ascites carcinoma (EAC) mouse model demonstrated that MMK-1931-loaded chitosomes (MMK-1931-Chitosomes) significantly suppressed tumour growth, as evidenced by substantial reductions in tumour volume and weight. They also activated apoptotic pathways, as demonstrated by the upregulation of Bax and caspase-9 and the downregulation of Bcl-2. Moreover, they modulated oncogenic signalling by reducing cyclin D and MDM2 levels while enhancing the expression of p53 and PTEN. Histopathological analysis confirmed widespread tumour necrosis and membrane damage. Notably, the antitumor efficacy of orally administered MMK-1931-Chitosomes was comparable to that of intraperitoneally delivered cisplatin, underscoring their potential as a safer, more patient-friendly alternative and establishing them as a promising oral nano-system for solid tumour therapy.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-18"},"PeriodicalIF":4.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic liposomes synergize with active molecules to enhance targeted therapy. 治疗性脂质体与活性分子协同作用，增强靶向治疗。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-17 DOI: 10.1080/1061186X.2025.2533336

Alireza Partoazar, Ramin Goudarzi, Ahmad Reza Dehpour

{"title":"Therapeutic liposomes synergize with active molecules to enhance targeted therapy.","authors":"Alireza Partoazar, Ramin Goudarzi, Ahmad Reza Dehpour","doi":"10.1080/1061186X.2025.2533336","DOIUrl":"10.1080/1061186X.2025.2533336","url":null,"abstract":"Liposomes composed of phospholipids (PLs) either alone or with an active molecule, can reveal a significant potential in the improvement of severe disorders such as Alzheimer's disease, osteoporosis, and inflammatory conditions. For instance, PLs exhibit anti-inflammatory, antioxidant, neuroprotective, and osteogenic properties in pathological conditions which accelerate the therapeutic effect of the drugs. These pharmacological properties can be modulated by the type and dose of PLs or liposome administration. They affect disorders through the signalling pathways, down or upregulation of gene expression, balance of oxidative stress, and other biological mechanisms. Interestingly, liposomes containing essential PLs like phosphatidylserine with active molecules such as curcumin or alendronate could synergistically improve certain diseases like osteoporosis in experimental models. Accordingly, we aimed to highlight the unique advantages of various PLs or liposomes with an emphasis on their diverse therapeutic modalities and potentiation of liposomes in synergy with the cargos in experimental studies. These properties suggest a promising approach to enhance drug efficacy and mitigate the side effects through reduced drug usage in chronic diseases, however, their clinical translation requires further validation of safety and effectiveness in human.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-9"},"PeriodicalIF":4.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Boosting breast cancer immunotherapy through targeted siRNA delivery and sequential chemotherapy. 通过靶向siRNA传递和序贯化疗促进乳腺癌免疫治疗。

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-17 DOI: 10.1080/1061186X.2025.2528921

Naghmeh Jabarimani, Ehsan Khabazian, Bahar Morshedi, Yousef Fatahi, Mina Hosseini, Farhad Jadidi Niaragh, Fatemeh Atyabi, Farid Dorkoosh

{"title":"Boosting breast cancer immunotherapy through targeted siRNA delivery and sequential chemotherapy.","authors":"Naghmeh Jabarimani, Ehsan Khabazian, Bahar Morshedi, Yousef Fatahi, Mina Hosseini, Farhad Jadidi Niaragh, Fatemeh Atyabi, Farid Dorkoosh","doi":"10.1080/1061186X.2025.2528921","DOIUrl":"10.1080/1061186X.2025.2528921","url":null,"abstract":"Cancer continues to be a major public health challenge due to therapeutic resistance, rising incidence and financial burden. Although anti-programmed cell death-ligand 1 (PD-L1) immunotherapy has revolutionised cancer treatment, its efficacy as monotherapy remains limited. Combining chemotherapy with immunotherapy offers the potential to amplify therapeutic outcomes and reduce side effects. Paclitaxel can induce immunogenic cell death (ICD) and improve tumour response to anti-PD-L1 therapy, thereby improving immunotherapy effectiveness. Meanwhile, small interfering RNA (siRNA) therapy can selectively suppress PD-L1 expression on the cell membrane and in the cytoplasm, though efficient delivery remains a challenge. We developed nanoparticles composed of trimethyl chitosan (TMC) and hyaluronic acid (HA) for delivering PD-L1 siRNA. These spherical nanoparticles (∼190 nm) demonstrated favourable physicochemical properties, high siRNA encapsulation efficiency, robust serum stability, a non-toxic nature and effective internalisation by cancer cells. The sequential therapy of sub-therapeutic doses of paclitaxel with siRNA PD-L1 in a 4T1 Balb/c mouse model compared to each monotherapy led to a substantial boost to antitumor immunity, suppression of tumour growth and increased infiltration of effector CD8+ T-cells within the tumour microenvironment. This study presents a novel siRNA delivery system and therapeutic approach that enhances the efficacy of breast cancer immunotherapy.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual AMPK activation and TXNIP suppression underlie the superior anti-diabetic action of rosiglitazone-metformin co-crystal (RZM): evidence from preclinical models. 双重AMPK激活和TXNIP抑制是罗格列酮-二甲双胍共晶（RZM）优越的抗糖尿病作用的基础：来自临床前模型的证据

IF 4.3 4区医学

Journal of Drug Targeting Pub Date : 2025-07-17 DOI: 10.1080/1061186X.2025.2534175

Leping Ruan, Yi Song, Gang Wang, Xiangnan Hu, Zongjie Gan, Weiying Zhou

{"title":"Dual AMPK activation and TXNIP suppression underlie the superior anti-diabetic action of rosiglitazone-metformin co-crystal (RZM): evidence from preclinical models.","authors":"Leping Ruan, Yi Song, Gang Wang, Xiangnan Hu, Zongjie Gan, Weiying Zhou","doi":"10.1080/1061186X.2025.2534175","DOIUrl":"10.1080/1061186X.2025.2534175","url":null,"abstract":"This study investigates the anti-diabetic potential of rosiglitazone-metformin adduct (RZM), a 1:1 molar co-crystal complex, in spontaneous diabetic KK mice and streptozotocin-induced diabetic rats. Diabetic models were divided into four groups: vehicle control, physical mixture (R + M), low-dose RZM, and high-dose RZM. Metabolic parameters including fasting glucose and lipid profiles were assessed over time, alongside hepatic histopathology and molecular analyses of AMPK/TXNIP pathways. In vitro validation employed high glucose-exposed MIN6 and INS-1 β-cells. RZM treatment significantly reduced hyperglycaemia, enhanced glucose tolerance, and ameliorated dyslipidemia, with dose-dependent efficacy. Histopathology demonstrated RZM's hepatoprotective effects through reduced steatosis and inflammation. Mechanistically, RZM activated AMPK phosphorylation while suppressing TXNIP overexpression in both pancreatic β-cells and metabolic tissues, a conserved pathway confirmed across species and in vitro models. Compared to conventional combination therapy, the stoichiometrically optimised RZM formulation exhibited superior glycemic control and liver protection via coordinated AMPK-TXNIP modulation. These findings establish RZM as a dual-targeting agent with translatable therapeutic advantages, providing preclinical evidence for its development as a next-generation antidiabetic drug through synergistic pathway regulation.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0