首页 > 最新文献

Journal of Drug Targeting最新文献

英文 中文
Drug screening approaches for small-molecule compounds in cancer-targeted therapy. 癌症靶向治疗中的小分子化合物药物筛选方法。
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2024-11-22 DOI: 10.1080/1061186X.2024.2427185
Yelin Zhao, Chenyu Yuan, Yuchen Shi, Xiaohong Liu, Liaoxin Luo, Li Zhang, Milica Pešić, Hongjuan Yao, Liang Li

Small-molecule compounds exhibit distinct pharmacological properties and clinical effectiveness. Over the past decade, advances in covalent drug discovery have led to successful small-molecule drugs, such as EGFR, BTK, and KRAS (G12C) inhibitors, for cancer therapy. Researchers are paying more attention to refining drug screening methods aiming for high throughput, fast speed, high specificity, and accuracy. Therefore, the discovery and development of small-molecule drugs has been facilitated by significantly reducing screening time and financial resources, and increasing promising lead compounds compared with traditional methods. This review aims to introduce classical and emerging methods for screening small-molecule compounds in targeted cancer therapy. It includes classification, principles, advantages, disadvantages, and successful applications, serving as valuable references for subsequent researchers.

小分子化合物具有独特的药理特性和临床疗效。在过去的十年中,共价药物发现技术的进步成功地开发出了用于癌症治疗的小分子药物,如表皮生长因子受体(EGFR)、BTK 和 KRAS (G12C) 抑制剂。研究人员越来越重视改进药物筛选方法,力求实现高通量、快速、高特异性和高准确性。因此,与传统方法相比,小分子药物的发现和开发大大缩短了筛选时间,减少了资金投入,增加了有前景的先导化合物。本综述旨在介绍癌症靶向治疗中筛选小分子化合物的经典方法和新兴方法。内容包括分类、原理、优缺点和成功应用,为后续研究人员提供有价值的参考。
{"title":"Drug screening approaches for small-molecule compounds in cancer-targeted therapy.","authors":"Yelin Zhao, Chenyu Yuan, Yuchen Shi, Xiaohong Liu, Liaoxin Luo, Li Zhang, Milica Pešić, Hongjuan Yao, Liang Li","doi":"10.1080/1061186X.2024.2427185","DOIUrl":"10.1080/1061186X.2024.2427185","url":null,"abstract":"<p><p>Small-molecule compounds exhibit distinct pharmacological properties and clinical effectiveness. Over the past decade, advances in covalent drug discovery have led to successful small-molecule drugs, such as EGFR, BTK, and KRAS (G12C) inhibitors, for cancer therapy. Researchers are paying more attention to refining drug screening methods aiming for high throughput, fast speed, high specificity, and accuracy. Therefore, the discovery and development of small-molecule drugs has been facilitated by significantly reducing screening time and financial resources, and increasing promising lead compounds compared with traditional methods. This review aims to introduce classical and emerging methods for screening small-molecule compounds in targeted cancer therapy. It includes classification, principles, advantages, disadvantages, and successful applications, serving as valuable references for subsequent researchers.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"368-383"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686939","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
Reversal potentials of Tween 20 in ABC transporter-mediated multidrug-resistant cancer and treatment-resistant depression through interacting with both drug-binding and ATP-binding areas on MDR proteins. 吐温 20 通过与 MDR 蛋白上的药物结合区和 ATP 结合区相互作用,逆转 ABC 转运体介导的多药耐药性癌症和耐药性抑郁症的潜能。
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-03-01 Epub Date: 2024-11-18 DOI: 10.1080/1061186X.2024.2429006
Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng

Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters in vitro and to evaluate its potential for overcoming drug resistance in two models: an in vitro cancer MDR model and an in vivo TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the in vivo depression-like behaviour model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both in vitro and in vivo, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.

药物外排转运体,尤其是那些属于 ATP 结合盒(ABC)转运体超家族的转运体,在各种耐药性问题中发挥着至关重要的作用,包括癌症中的多药耐药性(MDR)和重度抑郁症患者的耐药性抑郁症(TRD)。其中的关键转运体包括P-糖蛋白(P-gp)、多药耐药蛋白1(MRP1)和乳腺癌耐药蛋白(BCRP)。本研究旨在探讨聚氧乙烯(20)山梨糖醇酐单月桂酸酯(吐温 20)在体外对这些外流转运体的调节作用,并评估其在两种模型(体外癌症 MDR 模型和体内 TRD 模型)中克服耐药性的潜力。研究结果表明,0.001% 的吐温 20 能明显抑制所有三种转运体的外流作用。此外,0.005% 吐温 20 还能有效逆转各种癌症 MDR 细胞系对紫杉醇、长春新碱、多柔比星和米托蒽醌的耐药性。在体内抑郁样行为模型中,0.01% 吐温 20 明显增强了氟西汀的抗抑郁和抗焦虑作用。鉴于吐温 20 对 P-gp、MRP1 和 BCRP 有很强的抑制作用,而且在体外和体内都能逆转耐药性,因此它是解决转运体介导的耐药性问题的理想候选药物。
{"title":"Reversal potentials of Tween 20 in ABC transporter-mediated multidrug-resistant cancer and treatment-resistant depression through interacting with both drug-binding and ATP-binding areas on MDR proteins.","authors":"Yu-Cheng Ho, Wen-Chin Chiu, Jing-Yi Chen, Yu-Hsin Huang, Yu-Ning Teng","doi":"10.1080/1061186X.2024.2429006","DOIUrl":"10.1080/1061186X.2024.2429006","url":null,"abstract":"<p><p>Drug efflux transporters, especially those belonging to the ATP-binding cassette (ABC) transporter superfamily, play a crucial role in various drug resistance issues, including multidrug resistance (MDR) in cancer and treatment-resistant depression (TRD) in individuals with major depressive disorder. Key transporters in this context include P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). This study aimed to investigate the modulatory effects of polyoxyethylene (20) sorbitan monolaurate (Tween 20) on these efflux transporters <i>in vitro</i> and to evaluate its potential for overcoming drug resistance in two models: an <i>in vitro</i> cancer MDR model and an <i>in vivo</i> TRD model. The findings indicated that 0.001% Tween 20 significantly inhibited the efflux actions of all three transporters. Additionally, 0.005% Tween 20 effectively reversed resistance to paclitaxel, vincristine, doxorubicin, and mitoxantrone in various cancer MDR cell lines. In the <i>in vivo</i> depression-like behaviour model, 0.01% Tween 20 markedly enhanced the antidepressant and anxiolytic effects of fluoxetine. Given its strong inhibitory effects on P-gp, MRP1, and BCRP, along with its capacity to reverse drug resistance both <i>in vitro</i> and <i>in vivo</i>, Tween 20 is a compelling candidate for tackling transporter-mediated drug resistance.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"410-423"},"PeriodicalIF":4.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621810","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
Development and optimization of curcumin-loaded solid lipid nanoparticles using Box-Behnken design and evaluation of its efficacy in modulating morphine-induced conditioned place preference: in vivo and in silico studies.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-24 DOI: 10.1080/1061186X.2025.2468758
Amirhossein Babaei, Hossein Ebrahimi, Tina Shokouhi Kouchaksaraei, Seyyed Mohammad Hamidi, Mohadeseh Khazaeialiabad, Ali Siahposht-Khachaki, Pedram Ebrahimnejad

Drug addiction, particularly to opioids like morphine, remains a pressing global health issue. Curcumin, a natural flavonoid, holds promise for treating neurological disorders, yet faces challenges, such as poor solubility and limited bioavailability across the blood-brain barrier. Solid lipid nanoparticles offer a solution, facilitating drug delivery to the brain. Using the Box-Behnken design, nanoparticles were optimised, yielding particles sized 152 nm, with a polydispersity index of 0.254, and an encapsulation efficiency of 70.74%. These nanoparticles enhance curcumin concentration and retention in brain tissue. Behavioural experiments using the conditioned place preference (CPP) test confirmed curcumin's impact on morphine addiction and its modulation of c-Fos gene expression. Pharmacological network analysis identified potential mechanisms of action, highlighting common targets in calcium and serotonin pathways. Docking simulations showed curcumin's affinity for proteins like 5HT1A, MAO-A, and TRPV1, relevant to addiction pathways. This research underscores the potential of curcumin-loaded solid lipid nanoparticles as a therapeutic approach for combating opioid addiction and neurological disorders.

{"title":"Development and optimization of curcumin-loaded solid lipid nanoparticles using Box-Behnken design and evaluation of its efficacy in modulating morphine-induced conditioned place preference: <i>in vivo</i> and <i>in silico</i> studies.","authors":"Amirhossein Babaei, Hossein Ebrahimi, Tina Shokouhi Kouchaksaraei, Seyyed Mohammad Hamidi, Mohadeseh Khazaeialiabad, Ali Siahposht-Khachaki, Pedram Ebrahimnejad","doi":"10.1080/1061186X.2025.2468758","DOIUrl":"10.1080/1061186X.2025.2468758","url":null,"abstract":"<p><p>Drug addiction, particularly to opioids like morphine, remains a pressing global health issue. Curcumin, a natural flavonoid, holds promise for treating neurological disorders, yet faces challenges, such as poor solubility and limited bioavailability across the blood-brain barrier. Solid lipid nanoparticles offer a solution, facilitating drug delivery to the brain. Using the Box-Behnken design, nanoparticles were optimised, yielding particles sized 152 nm, with a polydispersity index of 0.254, and an encapsulation efficiency of 70.74%. These nanoparticles enhance curcumin concentration and retention in brain tissue. Behavioural experiments using the conditioned place preference (CPP) test confirmed curcumin's impact on morphine addiction and its modulation of c-Fos gene expression. Pharmacological network analysis identified potential mechanisms of action, highlighting common targets in calcium and serotonin pathways. Docking simulations showed curcumin's affinity for proteins like 5HT1A, MAO-A, and TRPV1, relevant to addiction pathways. This research underscores the potential of curcumin-loaded solid lipid nanoparticles as a therapeutic approach for combating opioid addiction and neurological disorders.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-22"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441115","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
Local delivery of ibrutinib by folate receptor-mediated targeting PLGA-PEG nanoparticles to glioblastoma multiform: in vitro and in vivo studies.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-24 DOI: 10.1080/1061186X.2025.2468749
Bahar Morshedi, Mehdi Esfandyari-Manesh, Fatemeh Atyabi, Mohammad Hossein Ghahremani, Rassoul Dinarvand

Glioblastoma multiforme (GBM) is a widespread and life-threatening kind of brain cancer, which has a high mortality rate. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, irreversibly adheres to a conserved cysteine residue of two enzymes BTK and BMX, inhibiting their kinase activities, which leads to suppression of the growth of glioma cells. This study synthesised PLGA-PEG-folate (PPF) polymer and subsequently encapsulated ibrutinib within PPF nanoparticles (IBT-PPF-NPs). H NMR spectra confirmed the synthesis of PPF polymer. The efficiency of IBT-PPF-NPs was 97 ± 2.26% with 8.8 ± 0.2% drug loading. The particle size was 208 ± 4.8 nm. The IC50 value of free ibrutinib, IB-PPF-NPs and ibrutinib encapsulated in PLGA NPs (IB-P-NPs) was 10.2, 7.6 and 10.13 µM in C6 cell lines, whereas in U-87 MG cells was 24.4, 16 and 25.2 µM, respectively. The cellular uptake of FITC-PPF-NPs increased from 47.6% to 90.3% in C6 cells and from 55% to 97.3% in U-87 MG cells compared to FITC-P-NPs. The in vivo results indicate a significant reduction in tumour size in treatment groups in comparison to control groups, while the group that received the intratumoural injection of IB-PPF-NPs exhibited a greater reduction. The folate-targeting agent enhances the nanoparticles' effectiveness by promoting their uptake through the endocytosis pathway.

{"title":"Local delivery of ibrutinib by folate receptor-mediated targeting PLGA-PEG nanoparticles to glioblastoma multiform: <i>in vitro</i> and <i>in vivo</i> studies.","authors":"Bahar Morshedi, Mehdi Esfandyari-Manesh, Fatemeh Atyabi, Mohammad Hossein Ghahremani, Rassoul Dinarvand","doi":"10.1080/1061186X.2025.2468749","DOIUrl":"10.1080/1061186X.2025.2468749","url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is a widespread and life-threatening kind of brain cancer, which has a high mortality rate. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, irreversibly adheres to a conserved cysteine residue of two enzymes BTK and BMX, inhibiting their kinase activities, which leads to suppression of the growth of glioma cells. This study synthesised PLGA-PEG-folate (PPF) polymer and subsequently encapsulated ibrutinib within PPF nanoparticles (IBT-PPF-NPs). H NMR spectra confirmed the synthesis of PPF polymer. The efficiency of IBT-PPF-NPs was 97 ± 2.26% with 8.8 ± 0.2% drug loading. The particle size was 208 ± 4.8 nm. The IC<sub>50</sub> value of free ibrutinib, IB-PPF-NPs and ibrutinib encapsulated in PLGA NPs (IB-P-NPs) was 10.2, 7.6 and 10.13 µM in C6 cell lines, whereas in U-87 MG cells was 24.4, 16 and 25.2 µM, respectively. The cellular uptake of FITC-PPF-NPs increased from 47.6% to 90.3% in C6 cells and from 55% to 97.3% in U-87 MG cells compared to FITC-P-NPs. The <i>in vivo</i> results indicate a significant reduction in tumour size in treatment groups in comparison to control groups, while the group that received the intratumoural injection of IB-PPF-NPs exhibited a greater reduction. The folate-targeting agent enhances the nanoparticles' effectiveness by promoting their uptake through the endocytosis pathway.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-16"},"PeriodicalIF":4.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441117","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
Preparation, in vitro and in vivo evaluation of phloretin-loaded TPGS/Pluronic F68 modified mixed micelles with enhanced bioavailability and anti-aging activity.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-23 DOI: 10.1080/1061186X.2025.2469753
Jiaying Li, Tingyuan Li, Mingjie Gong, Xiaowen Wang, Qinyang Hua, Xia Jiang, Qilong Wang, Elmurat Toreniyazov, Jiangnan Yu, Xia Cao, Michael Adu-Frimpong, Ximing Xu

Phloretin exhibits strong antioxidant and anti-aging properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterization revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-aging drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-aging effects of phloretin for broader clinical applications.

{"title":"Preparation, in vitro and in vivo evaluation of phloretin-loaded TPGS/Pluronic F68 modified mixed micelles with enhanced bioavailability and anti-aging activity.","authors":"Jiaying Li, Tingyuan Li, Mingjie Gong, Xiaowen Wang, Qinyang Hua, Xia Jiang, Qilong Wang, Elmurat Toreniyazov, Jiangnan Yu, Xia Cao, Michael Adu-Frimpong, Ximing Xu","doi":"10.1080/1061186X.2025.2469753","DOIUrl":"https://doi.org/10.1080/1061186X.2025.2469753","url":null,"abstract":"<p><p>Phloretin exhibits strong antioxidant and anti-aging properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterization revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-aging drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-aging effects of phloretin for broader clinical applications.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-45"},"PeriodicalIF":4.3,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483331","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
Development of linagliptin-loaded liposomes using aspartic acid conjugate for bone-targeted delivery to combat osteoporosis.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-21 DOI: 10.1080/1061186X.2025.2467089
Nikita Nirwan, Yakkala Prasanna Anjaneyulu, Yasmin Sultana, Divya Vohora

Osteoporosis is a common metabolic bone disorder that requires new treatment strategies. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a proven osteogenic agent in diabetes-linked bone loss. However, poor solubility, low oral bioavailability and inadequate bone-targeting limit its use in osteoporosis. We have successfully developed the bone-targeted liposomes of linagliptin using an aspartic acid conjugate, that is poly (aspartic acid-co-lactide)-1,2-dipalmitoyl-sn-glycero-3-phospho ethanolamine (PAL-DPPE), which was prior synthesised and identified using FTIR and NMR. Liposomes were evaluated for particle size, encapsulation efficacy, drug loading and release study in addition to in vitro hydroxyapatite binding ability. To determine the anti-osteoporosis effect of liposomes, in vivo testing was performed in glucocorticoid-induced osteoporosis model in mice. Bone targeted liposomes of linagliptin having particle size of 281.7 nm and hydroxyapatite affinity of 89% significantly improved the bone architecture parameters and bone mineral density in micro-computed tomography analysis. Further, these liposomes positively modulated sclerostin, bone morphogenetic protein-2, receptor activator of nuclear factor kappa beta/osteoprotegerin ratio and other bone turnover biomarkers. The findings demonstrate that aspartic acid conjugate (PAL-DPPE)-based bone-targeted liposomes of linagliptin hold promise for the treatment of osteoporosis. Moreover, the possible mechanistic pathways involved here is Wnt and AMPK pathway.

{"title":"Development of linagliptin-loaded liposomes using aspartic acid conjugate for bone-targeted delivery to combat osteoporosis.","authors":"Nikita Nirwan, Yakkala Prasanna Anjaneyulu, Yasmin Sultana, Divya Vohora","doi":"10.1080/1061186X.2025.2467089","DOIUrl":"10.1080/1061186X.2025.2467089","url":null,"abstract":"<p><p>Osteoporosis is a common metabolic bone disorder that requires new treatment strategies. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a proven osteogenic agent in diabetes-linked bone loss. However, poor solubility, low oral bioavailability and inadequate bone-targeting limit its use in osteoporosis. We have successfully developed the bone-targeted liposomes of linagliptin using an aspartic acid conjugate, that is poly (aspartic acid-co-lactide)-1,2-dipalmitoyl-sn-glycero-3-phospho ethanolamine (PAL-DPPE), which was prior synthesised and identified using FTIR and NMR. Liposomes were evaluated for particle size, encapsulation efficacy, drug loading and release study in addition to <i>in vitro</i> hydroxyapatite binding ability. To determine the anti-osteoporosis effect of liposomes, <i>in vivo</i> testing was performed in glucocorticoid-induced osteoporosis model in mice. Bone targeted liposomes of linagliptin having particle size of 281.7 nm and hydroxyapatite affinity of 89% significantly improved the bone architecture parameters and bone mineral density in micro-computed tomography analysis. Further, these liposomes positively modulated sclerostin, bone morphogenetic protein-2, receptor activator of nuclear factor kappa beta/osteoprotegerin ratio and other bone turnover biomarkers. The findings demonstrate that aspartic acid conjugate (PAL-DPPE)-based bone-targeted liposomes of linagliptin hold promise for the treatment of osteoporosis. Moreover, the possible mechanistic pathways involved here is Wnt and AMPK pathway.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408553","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
Anti-GPC3 antibody and cell-penetrating peptide CPP44 dual-ligand modified liposomes for targeted delivery of arsenic trioxide in the treatment of hepatocellular carcinoma.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-15 DOI: 10.1080/1061186X.2025.2461104
Congcong Lin, Jiamin Sun, Yun Yang, Xinyao Pan, Yifan Sun, Bin Sun, Chunli Gan

Arsenic trioxide (ATO), the active ingredient in Chinese arsenic, effectively inhibits hepatocellular carcinoma (HCC) cell growth, but its clinical application is limited by the lack of a targeted delivery system. Phosphatidylinositol proteoglycan 3 (GPC3) is specifically expressed in HCC, and CPP44 is a cell-penetrating peptide that targets HCC cells. Here, we developed a liposome incorporating ATO with dual surface modifications of anti-GPC3 antibody and CPP44. The system was firstly enriched and localised at the liver tumour site through passive targeting by EPR and active targeting by specific binding of anti-GPC3 antibody to GPC3 protein. CPP44 then facilitated ATO penetration into HCC cells. Specifically, we first employed computational modelling to demonstrate that the covalently-coupled antibody maintained its binding ability to the GPC3 antigen. Subsequent experimental assays revealed that Dl-ATO-Lp exhibited higher cell uptake rate and stronger tumour cell killing effect. In an HCC mouse model, Dl-ATO-Lp achieved effective tumour targeting, with a tumour inhibition rate of 63.43%. This dual-ligand liposome system enhances the targeted delivery and therapeutic efficacy of ATO, offering a promising direction for solid tumour therapy and advancing the clinical application of ATO.

{"title":"Anti-GPC3 antibody and cell-penetrating peptide CPP44 dual-ligand modified liposomes for targeted delivery of arsenic trioxide in the treatment of hepatocellular carcinoma.","authors":"Congcong Lin, Jiamin Sun, Yun Yang, Xinyao Pan, Yifan Sun, Bin Sun, Chunli Gan","doi":"10.1080/1061186X.2025.2461104","DOIUrl":"10.1080/1061186X.2025.2461104","url":null,"abstract":"<p><p>Arsenic trioxide (ATO), the active ingredient in Chinese arsenic, effectively inhibits hepatocellular carcinoma (HCC) cell growth, but its clinical application is limited by the lack of a targeted delivery system. Phosphatidylinositol proteoglycan 3 (GPC3) is specifically expressed in HCC, and CPP44 is a cell-penetrating peptide that targets HCC cells. Here, we developed a liposome incorporating ATO with dual surface modifications of anti-GPC3 antibody and CPP44. The system was firstly enriched and localised at the liver tumour site through passive targeting by EPR and active targeting by specific binding of anti-GPC3 antibody to GPC3 protein. CPP44 then facilitated ATO penetration into HCC cells. Specifically, we first employed computational modelling to demonstrate that the covalently-coupled antibody maintained its binding ability to the GPC3 antigen. Subsequent experimental assays revealed that Dl-ATO-Lp exhibited higher cell uptake rate and stronger tumour cell killing effect. In an HCC mouse model, Dl-ATO-Lp achieved effective tumour targeting, with a tumour inhibition rate of 63.43%. This dual-ligand liposome system enhances the targeted delivery and therapeutic efficacy of ATO, offering a promising direction for solid tumour therapy and advancing the clinical application of ATO.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066008","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
Molecular and therapeutic insight into ER stress signalling in NSCLC.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-14 DOI: 10.1080/1061186X.2025.2461105
Aastha Jadhav, Arjun Menon, Kush Gupta, Neeru Singh

Endoplasmic Reticulum (ER) stress is intricately involved in cancer development, progression and response to chemotherapy. ER stress related genes might play an important role in predicting the prognosis in lung adenocarcinoma patients and may be manipulated to improve the treatment outcome and overall survival rate. In this review, we analysed the contribution of the three major ER stress pathways-IRE1, ATF6, and PERK-in lung cancer pathogenesis via modulation of tumour microenvironment (TME) and processes as metastasis, angiogenesis, apoptosis and N-glycosylation. Furthermore, we discuss the regulatory role of microRNAs in fine-tuning ER stress pathways in Non-Small Cell Lung Cancer (NSCLC). Our review also highlights various promising strategies to overcome chemoresistance by targeting ER stress pathways, offering new therapeutic opportunities.

{"title":"Molecular and therapeutic insight into ER stress signalling in NSCLC.","authors":"Aastha Jadhav, Arjun Menon, Kush Gupta, Neeru Singh","doi":"10.1080/1061186X.2025.2461105","DOIUrl":"10.1080/1061186X.2025.2461105","url":null,"abstract":"<p><p>Endoplasmic Reticulum (ER) stress is intricately involved in cancer development, progression and response to chemotherapy. ER stress related genes might play an important role in predicting the prognosis in lung adenocarcinoma patients and may be manipulated to improve the treatment outcome and overall survival rate. In this review, we analysed the contribution of the three major ER stress pathways-IRE1, ATF6, and PERK-in lung cancer pathogenesis <i>via</i> modulation of tumour microenvironment (TME) and processes as metastasis, angiogenesis, apoptosis and N-glycosylation. Furthermore, we discuss the regulatory role of microRNAs in fine-tuning ER stress pathways in Non-Small Cell Lung Cancer (NSCLC). Our review also highlights various promising strategies to overcome chemoresistance by targeting ER stress pathways, offering new therapeutic opportunities.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":4.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066011","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
Pseudo-ternary phase diagram based PEGylated nano-dispersion of linezolid to promote wound regeneration: an in vitro and in vivo evaluation.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-12 DOI: 10.1080/1061186X.2025.2461093
Bani Kumar Jana, Ishita Singha, Nusalu Puro, Rinku Baishya, Rajat Subhra Dutta, Mohini Singh, Bhaskar Mazumder

Open wounds are prone to bacterial infiltration mostly resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), which affects healing of open wounds. Topical linezolid nano-dispersion using essential oils as nanoemulgel can increase solubility of drug and bypass side-effects like GI-irritation of oral administration. Pseudo-ternary phase diagram was built to optimise nanoemulsion. Surfactant/co-surfactant mixture (3:1), deionised water and Oilmix (4:1) with drug were vortexed and then ultrasonicated. 1% carbopol gel of optimised nanoemulsion was prepared and characterised, exposed to antimicrobial study, cytocompatibility study using HEK293 cell-line, and in vivo wound healing study using rat excision model. Histological study was performed to confirm growth of stratum corneum. Optimised formulation has particle size (244.6 ± 178.66 nm), polydispersity index (25%), entrapment efficiency (92.3 ± 3.38%) and in vitro drug release (87.58 ± 4.16%) best fitted in Korsmeyer-Peppas kinetics model. Nanoemulgel F6 (0.2%w/w) was found with viscosity of 5345 ± 6 cP constituting a very excellent antimicrobial effect against MRSA. HEK293 cells had shown good cytocompatibility with formulation. The wound contraction rate was 99.66 ± 0.57% at day 15 on daily application of nanoemulgel and stratum corneum was almost fully regenerated. The developed nanoemulgel has potential antimicrobial efficacy and can promote wound healing.

{"title":"Pseudo-ternary phase diagram based PEGylated nano-dispersion of linezolid to promote wound regeneration: an <i>in vitro</i> and <i>in vivo</i> evaluation.","authors":"Bani Kumar Jana, Ishita Singha, Nusalu Puro, Rinku Baishya, Rajat Subhra Dutta, Mohini Singh, Bhaskar Mazumder","doi":"10.1080/1061186X.2025.2461093","DOIUrl":"10.1080/1061186X.2025.2461093","url":null,"abstract":"<p><p>Open wounds are prone to bacterial infiltration mostly resistant strains like methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), which affects healing of open wounds. Topical linezolid nano-dispersion using essential oils as nanoemulgel can increase solubility of drug and bypass side-effects like GI-irritation of oral administration. Pseudo-ternary phase diagram was built to optimise nanoemulsion. Surfactant/co-surfactant mixture (3:1), deionised water and Oil<sub>mix</sub> (4:1) with drug were vortexed and then ultrasonicated. 1% carbopol gel of optimised nanoemulsion was prepared and characterised, exposed to antimicrobial study, cytocompatibility study using HEK293 cell-line, and <i>in vivo</i> wound healing study using rat excision model. Histological study was performed to confirm growth of stratum corneum. Optimised formulation has particle size (244.6 ± 178.66 nm), polydispersity index (25%), entrapment efficiency (92.3 ± 3.38%) and <i>in vitro</i> drug release (87.58 ± 4.16%) best fitted in Korsmeyer-Peppas kinetics model. Nanoemulgel F6 (0.2%w/w) was found with viscosity of 5345 ± 6 cP constituting a very excellent antimicrobial effect against MRSA. HEK293 cells had shown good cytocompatibility with formulation. The wound contraction rate was 99.66 ± 0.57% at day 15 on daily application of nanoemulgel and stratum corneum was almost fully regenerated. The developed nanoemulgel has potential antimicrobial efficacy and can promote wound healing.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-15"},"PeriodicalIF":4.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074505","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 role of green synthesis metal and metal oxide nanoparticles in oral cancer therapy: a review.
IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2025-02-08 DOI: 10.1080/1061186X.2025.2461091
Songlin Zhou, Yutao Qin, Anwen Lei, Hai Liu, Yi Sun, Jue Zhang, Chao Deng, Yu Chen

There are 275,000 new cases of oral cancer (OC) per year, making it the sixth most common cancer in the world. Severe adverse effects, including loss of function, deformity, and systemic toxicity, are familiar with traditional therapies such as radiation, chemotherapy, and surgery; due to their unique properties, nanoparticles (NPs) have emerged as a superior alternative over chemo/radiotherapy and surgery due to their targeting capability, bioavailability, compatibility, and high solubility. Due to their unique properties, metallic NPs have garnered significant attention in OC control. In addition to the fact that metal NPs may be harmful to human cells, the reactive chemicals used to make them pose the same risk, which limits their use in medicine. Green synthesis (GS) is a novel strategy that uses biological materials like yeast, bacteria, fungi, and plant extracts. Compared to more traditional chemical synthesis processes, these are more environmentally benign and manageable for living organisms. This article summarises the GS of NPs made of metals and metal oxides and their anticancer effects on OC. The method's potential benefits and drawbacks in advancing metallic NPs' GS and shaping OC therapy's future were also discussed.

{"title":"The role of green synthesis metal and metal oxide nanoparticles in oral cancer therapy: a review.","authors":"Songlin Zhou, Yutao Qin, Anwen Lei, Hai Liu, Yi Sun, Jue Zhang, Chao Deng, Yu Chen","doi":"10.1080/1061186X.2025.2461091","DOIUrl":"10.1080/1061186X.2025.2461091","url":null,"abstract":"<p><p>There are 275,000 new cases of oral cancer (OC) per year, making it the sixth most common cancer in the world. Severe adverse effects, including loss of function, deformity, and systemic toxicity, are familiar with traditional therapies such as radiation, chemotherapy, and surgery; due to their unique properties, nanoparticles (NPs) have emerged as a superior alternative over chemo/radiotherapy and surgery due to their targeting capability, bioavailability, compatibility, and high solubility. Due to their unique properties, metallic NPs have garnered significant attention in OC control. In addition to the fact that metal NPs may be harmful to human cells, the reactive chemicals used to make them pose the same risk, which limits their use in medicine. Green synthesis (GS) is a novel strategy that uses biological materials like yeast, bacteria, fungi, and plant extracts. Compared to more traditional chemical synthesis processes, these are more environmentally benign and manageable for living organisms. This article summarises the GS of NPs made of metals and metal oxides and their anticancer effects on OC. The method's potential benefits and drawbacks in advancing metallic NPs' GS and shaping OC therapy's future were also discussed.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-24"},"PeriodicalIF":4.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066013","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
期刊
Journal of Drug Targeting
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1