Journal of Drug Targeting最新文献

{"title":"Nano-medicine therapy reprogramming metabolic network of tumour microenvironment: new opportunity for cancer therapies.","authors":"Xiaojie Zhang, Min An, Juntao Zhang, Yumeng Zhao, Yanhua Liu","doi":"10.1080/1061186X.2024.2309565","DOIUrl":"10.1080/1061186X.2024.2309565","url":null,"abstract":"<p><p>Metabolic heterogeneity is one of the characteristics of tumour cells. In order to adapt to the tumour microenvironment of hypoxia, acidity and nutritional deficiency, tumour cells have undergone extensive metabolic reprogramming. Metabolites involved in tumour cell metabolism are also very different from normal cells, such as a large number of lactate and adenosine. Metabolites play an important role in regulating the whole tumour microenvironment. Taking metabolites as the target, it aims to change the metabolic pattern of tumour cells again, destroy the energy balance it maintains, activate the immune system, and finally kill tumour cells. In this paper, the regulatory effects of metabolites such as lactate, glutamine, arginine, tryptophan, fatty acids and adenosine were reviewed, and the related targeting strategies of nano-medicines were summarised, and the future therapeutic strategies of nano-drugs were discussed. The abnormality of tumour metabolites caused by tumour metabolic remodelling not only changes the energy and material supply of tumour, but also participates in the regulation of tumour-related signal pathways, which plays an important role in the survival, proliferation, invasion and metastasis of tumour cells. Regulating the availability of local metabolites is a new aspect that affects tumour progress. (The graphical abstract is by Figdraw).</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"241-257"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512536","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}

{"title":"Colon-targeted delivery of niclosamide from solid dispersion employing a pH-dependent polymer via hotmelt extrusion for the treatment of ulcerative colitis in mice.","authors":"Sakshi Arjun, Uttam Kulhari, Amruta Prabhakar Padakanti, Bidya Dhar Sahu, Naveen Chella","doi":"10.1080/1061186X.2023.2298849","DOIUrl":"10.1080/1061186X.2023.2298849","url":null,"abstract":"<p><p>Niclosamide (NCL) is repurposed to treat inflammatory bowel disease due to its anti-inflammatory properties and potential to reduce oxidative stress. This therapeutic activity remains challenging if administered directly due to its low solubility and high recrystallization tendency in gastric pH. Solid dispersions using pH-dependent polymer will be a better idea to improve the solubility, dissolution and targeted delivery at the colon. Hot melt extrusion was used to formulate a solid dispersion with 30% NCL utilising hydroxypropyl methylcellulose acetate succinate as a pH-dependent polymer. <i>In vitro</i> drug release studies revealed formulation (F1) containing 10%w/w Tween 80 showed minimal release (2.06%) at the end of 2 h, followed by 47.87% and 82.15% drug release at 6 h and 14 h, respectively, indicating the maximum amount of drug release in the colon. The drug release from the formulations containing no plasticiser and 5%w/w plasticiser was comparable to the pure crystalline drug (approximately 25%). Solid-state analysis confirmed particle conversion of crystalline NCL to amorphous form, and the optimised formulation was stable for 6 months without significant changes in dissolution profile. In contrast to pure NCL, the F1 formulation substantially reduced the disease activity index, colonic inflammation, histological alterations and oxidative damage in colitis mice. These findings reveal that the prepared formulation can potentially deliver the drug locally at the colon, making it an effective tool in treating ulcerative colitis.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"186-199"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830041","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}

{"title":"Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A.","authors":"Yongpeng Wei, Guangyao Li, Zhuo Wang, Kewen Qian, Shuyi Zhang, Lingling Zhang, Changhai Lei, Shi Hu","doi":"10.1080/1061186X.2023.2301418","DOIUrl":"10.1080/1061186X.2023.2301418","url":null,"abstract":"<p><p>Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy. The scFv small-molecular single-chain antibody sequenced, designed, constructed, expressed and purified by hybridoma has high neutralising activity and affinity level, which can lay a good foundation for the modification and development of antibody engineering drugs. <i>In vivo</i> experiments, AAV-mediated scFv engineering drug has good anti-BONT/A toxin neutralisation ability, has advantages of simple operation, stable expression and good efficacy, and may be one of the effective treatment strategies for long-term prevention and protection of BONT/A botulinum neurotoxin.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"213-222"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074264","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}

{"title":"Machine learning for skin permeability prediction: random forest and XG boost regression.","authors":"Kevin Ita, Joyce Prinze","doi":"10.1080/1061186X.2023.2284096","DOIUrl":"10.1080/1061186X.2023.2284096","url":null,"abstract":"<p><p><b>Background:</b> Machine learning algorithms that can quickly and easily estimate skin permeability (Kp) are increasingly being used in drug delivery research. The linear free energy relationship (LFER) developed by Abraham is a practical technique for predicting Kp. The permeability coefficients and Abraham solute descriptor values for 175 organic compounds have been documented in the scientific literature.<b>Purpose:</b> The purpose of this project was to use a publicly available dataset to make skin permeability predictions using the random forest and XBoost regression techniques.<b>Methods:</b> We employed Pandas-based methods in JupyterLab to predict permeability coefficient (Kp) from solute descriptors (excess molar refraction [E], combined dipolarity/polarizability [S], overall solute hydrogen bond acidity and basicity [A and B], and the McGowan's characteristic molecular volume [V]).<b>Results:</b> The random forest and XG Boost regression models established statistically significant association between the descriptors and the skin permeability coefficient.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"57-65"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92154715","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}

{"title":"Antibody-drug conjugates targeting DDR1 as a novel strategy for treatment of breast cancer.","authors":"Yiran Tao, Ying Lu, Ting Xue, Qinhuai Lai, Hengrui Song, Xiaofeng Chen, Cuiyu Guo, Jinliang Yang, Yuxi Wang","doi":"10.1080/1061186X.2024.2386621","DOIUrl":"10.1080/1061186X.2024.2386621","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have emerged as a novel class of targeted cancer therapies and been successfully applied in the treatment of breast cancer (BC). Discoidin domain receptor 1 (DDR1) is a single transmembrane receptor tyrosine kinase and has been identified as a possible target for cancer. In this study, we explored the potential of an anti-DDR1 ADC, named T₄H₁₁-DM4, for the treatment of DDR1-positive BC. We demonstrated that high protein expression and RNA expression of DDR1 in BC tissues. <i>In vitro</i>, T₄H₁₁-DM4 was potently cytotoxic to DDR1-expressing BC cells, with IC50 in the nanomolar range. In mice BC xenograft models, T₄H₁₁-DM4 dramatically eliminated BC tumours, without observable toxicity. Taken together, our findings demonstrated that DDR1 can serve as a promising therapeutic target for BC.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1295-1304"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788240","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}

{"title":"Laser-enzyme dual responsive liposomes to regulate autophagy in synergy with phototherapy for melanoma treatment.","authors":"Mingli Sui, Chaoqun Wang, Yingmei Tian, Huijuan Zhang","doi":"10.1080/1061186X.2024.2386624","DOIUrl":"10.1080/1061186X.2024.2386624","url":null,"abstract":"<p><p>Phototherapy can cause autophagy while killing tumour cells, leading to tumour recurrence and metastasis. Here, we constructed a laser and enzyme dual responsive nanodrug delivery system Tf-Te@CTSL-HCQ (TT@CH) to precisely regulate autophagy in synergy with phototherapy to inhibit the proliferation and metastasis of melanoma. Firstly, transferrin (Tf) was used as a nanoreactor to synthesise phototherapy agent Tf-Te by the biological template mineralisation method. Then, the thermosensitive liposome modified with FAP-α-responsive peptide (CAP) was used as a carrier to encapsulate autophagy inhibitor hydroxychloroquine (HCQ) and Tf-Te, to obtain an intelligent TT@CH delivery system. Once arriving at the tumour site, TT@CH can be cleaved by FAP-α overexpressed on cancer-associated fibroblasts (CAFs), and release Tf-Te and HCQ. Then Tf-Te can target melanoma cells and exert PTT/PDT anti-tumour effect. What's more, hyperpyrexia induced by PTT can further promote drugs release from TT@CH. Meanwhile, HCQ simultaneously inhibited autophagy of CAFs and melanoma cells, and down-regulated IL-6 and HMGB1 secretion, thus effectively inhibiting melanoma metastasis. Pharmacodynamic results exhibited the best anti-tumour effect of TT@CH with the highest tumour inhibition rate of 91.3%. Meanwhile, lung metastatic nodules of TT@CH treated mice reduced by 124.33 compared with that of mice in control group. Overall, TT@CH provided an effective therapy strategy for melanoma.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1305-1319"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788241","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}

{"title":"Liver-targeted delivery based on prodrug: passive and active approaches.","authors":"Jiaqi Chen, Yingrui Yao, Xiaoran Mao, Yuzhou Chen, Feng Ni","doi":"10.1080/1061186X.2024.2386416","DOIUrl":"10.1080/1061186X.2024.2386416","url":null,"abstract":"<p><strong>Background: </strong>The liver, a central organ in human metabolism, is often the primary target for drugs. However, conditions such as viral hepatitis, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC) present substantial health challenges worldwide. Existing treatments, which suffer from the non-specific distribution of drugs, frequently fail to achieve desired efficacy and safety, risking unnecessary liver harm and systemic side effects.</p><p><strong>Purpose: </strong>The aim of this review is to synthesise the latest progress in the design of liver-targeted prodrugs, with a focus on passive and active targeting strategies, providing new insights into the development of liver-targeted therapeutic approaches.</p><p><strong>Methods: </strong>This study conducted an extensive literature search through databases like Google Scholar, PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), systematically collecting and selecting recent research on liver-targeted prodrugs. The focus was on targeting mechanisms, including the Enhanced Permeability and Retention (EPR) effect, the unique microenvironment of liver cancer, and active targeting through specific transporters and receptors.</p><p><strong>Results: </strong>Active targeting strategies achieve precise drug delivery by binding specific ligands to liver surface receptors. Passive targeting takes advantage of the EPR effect and tumour characteristics to enrich drugs in liver tumours. The review details successful cases of using small molecule ligands, peptides, antibodies and nanoparticles as drug carriers.</p><p><strong>Conclusion: </strong>Liver-targeted prodrug strategies show great potential in enhancing the efficacy of drug treatment and reducing side effects for liver diseases. Future research should balance the advantages and limitations of both targeting strategies, focusing on optimising drug design and targeting efficiency, especially for clinical application. In-depth research on liver-specific receptors and the development of innovative targeting molecules are crucial for advancing the field of liver-targeted prodrugs.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1155-1168"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788242","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}

{"title":"Clinical evaluation of liposome-based gel formulation containing glycolic acid for the treatment of photodamaged skin.","authors":"Eskandar Moghimipour, Ali Gorji, Reza Yaghoobi, Anayatollah Salimi, Mahmoud Latifi, Maryam Aghakouchakzadeh, Somayeh Handali","doi":"10.1080/1061186X.2023.2288998","DOIUrl":"10.1080/1061186X.2023.2288998","url":null,"abstract":"<p><p><b>Background:</b> Long contact of UV causes skin damage. Glycolic acid (GA) as an alpha hydroxy acid is used to treat photodamaged skin. However, GA leads to side effects including; burning, erythema and peeling.<b>Purpose:</b> The aim of this study was to develop a controlled delivery systems loading GA in order to increasing its efficacy and lowering its side effects.<b>Methods:</b> Liposomes were evaluated for encapsulation efficiency, size and morphology. Optimized formulation was dispersed in HPMC gel bases and drug release kinetics were also studied. Clinical efficacy and safety of GA-loaded liposomal gel and GA gel formulation were evaluated in patients with photodamaged skin.<b>Results:</b> The EE% and average particle size of liposomes were 64 ±2.1 % and 317±3.6 nm, respectively. SEM image showed that liposomes were spherical in shape. In vitro release kinetics of GA from both formulations followed Weibull model. Clinical evaluation revealed that GA-loaded liposomal gel was more effective than GA gel formulation. Treatment with GA-loaded liposomal gel resulted in a statistically significant reduction in the scores of hyperpigmentation, fine wrinkling and lentigines. Moreover, liposomal gel formulation was able to minimize side effects of GA.<b>Conclusion:</b> According to the obtained results, the liposome-based gel formulation can be used as potential drug delivery system to enhance permeation of GA through skin layers and also reduce its side effects.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"74-79"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444876","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}

{"title":"A cisplatin and disulphiram co-loaded inclusion complex overcomes drug resistance by inhibiting cancer cell stemness in non-small cell lung cancer.","authors":"Wenhui Ye, Huaiyou Lv, Qinxiu Zhang, Jianxiong Zhao, Xin Zhao, Guozhi Zhao, Chongzheng Yan, Fengqin Sun, Zhongxi Zhao, Xiumei Jia","doi":"10.1080/1061186X.2023.2298844","DOIUrl":"10.1080/1061186X.2023.2298844","url":null,"abstract":"<p><p><b>Introduction:</b> Non-small cell lung cancer (NSCLC) accounting for about 80-85% of all lung cancer cases is one of the fastest-growing malignancies in terms of incidence and mortality worldwide and is commonly treated with cisplatin (DDP). Although treatment may initially be effective, the DDP therapy often leads to the development of chemoresistance and treatment failure. Disulphiram (DSF), an old alcohol-aversion drug, has been revealed to help reverse drug resistance in several cancers. In addition, several studies have shown a close relationship between drug resistance and cancer cell stemness.<b>Methods:</b> In this study, DDP and DSF were embedded in hydroxypropyl-β-cyclodextrin (CD) to prepare a co-loaded inclusion complex of DDP and DSF (DDP-DSF/CD) with enhanced solubility and therapeutic effects. The effects and mechanism of DSF on the DDP resistance from the perspective of cancer cell stemness were determined.<b>Results:</b> Our data show that DDP-DSF/CD increased cytotoxicity and apoptosis of DDP-resistant A549 (A549/DDP) cells, inhibited stem cell transcriptional regulatory genes and drug resistance-associated proteins and reversed the DDP resistance <i>in vitro</i> and <i>in vivo</i>.<b>Discussion:</b> Overall, DDP-DSF/CD could be a promising formulation for the reversal of DDP resistance in NSCLC by inhibiting cancer cell stemness.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"159-171"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830040","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}

{"title":"Advances in herbal polysaccharides-based nano-drug delivery systems for cancer immunotherapy.","authors":"Miao-Miao Han, Yi-Kai Fan, Yun Zhang, Zheng-Qi Dong","doi":"10.1080/1061186X.2024.2309661","DOIUrl":"10.1080/1061186X.2024.2309661","url":null,"abstract":"<p><p>The boom in cancer immunotherapy has provided many patients with a better chance of survival, but opportunities often come with challenges. Single immunotherapy is not good enough to eradicate tumours, and often fails to achieve the desired therapeutic effect because of the low targeting of immunotherapy drugs, and causes more side effects. As a solution to this problem, researchers have developed several nano Drug Delivery Systems (NDDS) to deliver immunotherapeutic agents to achieve good therapeutic outcomes. However, traditional drug delivery systems (DDS) have disadvantages such as poor bioavailability, high cytotoxicity, and difficulty in synthesis, etc. Herbal Polysaccharides (HPS), derived from natural Chinese herbs, inherently possess low toxicity. Furthermore, the biocompatibility, biodegradability, hydrophilicity, ease of modification, and immunomodulatory activities of HPS offer unique advantages in substituting traditional DDS. This review initially addresses the current developments and challenges in immunotherapy. Subsequently, it focuses on the immunomodulatory mechanisms of HPS and their design as nanomedicines for targeted drug delivery in tumour immunotherapy. Our findings reveal that HPS-based nanomedicines exhibit significant potential in enhancing the efficacy of cancer immunotherapy, providing crucial theoretical foundations and practical guidelines for future clinical applications.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"311-324"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545667","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}