Journal of Drug TargetingPub Date : 2025-07-01Epub Date: 2025-02-04DOI: 10.1080/1061186X.2025.2458616
Yuanyuan Li, Baojie Du, Lichao Yu, Hong Luo, Haibo Rong, Xiangdong Gao, Jun Yin
{"title":"Strategies and challenges of cytosolic delivery of proteins.","authors":"Yuanyuan Li, Baojie Du, Lichao Yu, Hong Luo, Haibo Rong, Xiangdong Gao, Jun Yin","doi":"10.1080/1061186X.2025.2458616","DOIUrl":"10.1080/1061186X.2025.2458616","url":null,"abstract":"<p><p>The cytosolic delivery of therapeutic proteins represents a promising strategy for addressing diseases caused by protein dysfunction. Despite significant advances, efficient delivery remains challenging due to barriers such as cell membrane impermeability, endosomal sequestration and protein instability. This review summarises recent progress in protein delivery systems, including physical, chemical and biological approaches, with a particular focus on strategies that enhance endosomal escape and targeting specificity. We further discuss the clinical translatability of these approaches and propose future directions for improving delivery efficiency and safety, ultimately unlocking the therapeutic potential of intracellular proteins.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"837-852"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039242","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":"Role of liposomes in chemoimmunotherapy of breast cancer.","authors":"Fatemeh Attarian, Ghazaleh Hatamian, Shamim Nosrati, Mahsa Akbari Oryani, Hossein Javid, Alireza Hashemzadeh, Mojtaba Tarin","doi":"10.1080/1061186X.2025.2467139","DOIUrl":"10.1080/1061186X.2025.2467139","url":null,"abstract":"<p><p>In the dynamic arena of cancer therapeutics, chemoimmunotherapy has shown tremendous promise, especially for aggressive forms of breast cancer like triple-negative breast cancer (TNBC). This review delves into the significant role of liposomes in enhancing the effectiveness of chemoimmunotherapy by leveraging breast cancer-specific mechanisms such as the induction of immunogenic cell death (ICD), reprogramming the tumour microenvironment (TME), and enabling sequential drug release. We examine innovative dual-targeting liposomes that capitalise on tumour heterogeneity, as well as pH-sensitive formulations that offer improved control over drug delivery. Unlike prior analyses, this review directly links advancements in preclinical research-such as PAMAM dendrimer-based nanoplatforms and RGD-decorated liposomes-to clinical trial results, highlighting their potential to revolutionise TNBC treatment strategies. Additionally, we address ongoing challenges related to scalability, toxicity, and regulatory compliance, and propose future directions for personalised, immune-focused nanomedicine. This work not only synthesises the latest research but also offers a framework for translating liposomal chemoimmunotherapy from laboratory research to clinical practice.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"887-915"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449167","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 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":"1014-1025"},"PeriodicalIF":4.3,"publicationDate":"2025-07-01","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}
{"title":"Advancements in colorectal cancer immunotherapy: from CAR-T cells to exosome-based therapies.","authors":"Sepideh Arabi, Manouchehr Fadaee, Tohid Kazemi, Mohammadreza Rahmani","doi":"10.1080/1061186X.2024.2449482","DOIUrl":"10.1080/1061186X.2024.2449482","url":null,"abstract":"<p><p>Colorectal cancer (CRC) continues to be a major worldwide health issue, with elevated death rates linked to late stages of the illness. Immunotherapy has made significant progress in developing effective techniques to improve the immune system's capacity to identify and eradicate cancerous cells. This study examines the most recent advancements in CAR-T cell treatment and exosome-based immunotherapy for CRC. CAR-T cell therapy, although effective in treating blood cancers, encounters obstacles when used against solid tumours such as CRC. These obstacles include the presence of an immunosuppressive tumour microenvironment and a scarcity of tumour-specific antigens. Nevertheless, novel strategies like dual-receptor CAR-T cells and combination therapy involving cytokines have demonstrated promise in surmounting these obstacles. Exosome-based immunotherapy is a promising approach for targeted delivery of therapeutic drugs to tumour cells, with high specificity and minimal off-target effects. However, there are still obstacles to overcome in the field, such as resistance to treatment, adverse effects associated with the immune system, and the necessity for more individualised methods. The current research is focused on enhancing these therapies, enhancing the results for patients, and ultimately incorporating these innovative immunotherapeutic approaches into the standard treatment protocols for CRC.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"749-760"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927339","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 nanomedicine for retinal drug delivery: overcoming barriers and enhancing therapeutic outcomes.","authors":"Pratikeswar Panda, Shreyashree Mohanty, Sangita Ranee Gouda, Rajaram Mohapatra","doi":"10.1080/1061186X.2024.2443144","DOIUrl":"10.1080/1061186X.2024.2443144","url":null,"abstract":"<p><p>Nanomedicine offers a promising avenue for improving retinal drug delivery, effectively addressing challenges associated with ocular diseases like age-related macular degeneration and diabetic retinopathy. Nanoparticles, with their submicron size and customisable surface properties, enable enhanced permeability and retention within retinal tissues, supporting sustained drug release and minimising systemic side effects. Nanostructured scaffolds further provide a supportive environment for retinal cell growth and tissue regeneration, crucial for treating degenerative conditions. Additionally, advanced nanodevices facilitate real-time monitoring and controlled drug release, marking significant progress in retinal therapy. This study reviews recent advancements in nanomedicine for retinal drug delivery, critically analysing design innovations, therapeutic benefits, and limitations of these systems. By advancing nanotechnology integration in ocular therapies, this field holds strong potential for overcoming current barriers, ultimately improving patient outcomes and quality of life.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"587-611"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854360","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":"The biomedical applications of artificial intelligence: an overview of decades of research.","authors":"Sweet Naskar, Suraj Sharma, Ketousetuo Kuotsu, Suman Halder, Goutam Pal, Subhankar Saha, Shubhadeep Mondal, Ujjwal Kumar Biswas, Mayukh Jana, Sunirmal Bhattacharjee","doi":"10.1080/1061186X.2024.2448711","DOIUrl":"10.1080/1061186X.2024.2448711","url":null,"abstract":"<p><p>A significant area of computer science called artificial intelligence (AI) is successfully applied to the analysis of intricate biological data and the extraction of substantial associations from datasets for a variety of biomedical uses. AI has attracted significant interest in biomedical research due to its features: (i) better patient care through early diagnosis and detection; (ii) enhanced workflow; (iii) lowering medical errors; (v) lowering medical costs; (vi) reducing morbidity and mortality; (vii) enhancing performance; (viii) enhancing precision; and (ix) time efficiency. Quantitative metrics are crucial for evaluating AI implementations, providing insights, enabling informed decisions, and measuring the impact of AI-driven initiatives, thereby enhancing transparency, accountability, and overall impact. The implementation of AI in biomedical fields faces challenges such as ethical and privacy concerns, lack of awareness, technology unreliability, and professional liability. A brief discussion is given of the AI techniques, which include Virtual screening (VS), DL, ML, Hidden Markov models (HMMs), Neural networks (NNs), Generative models (GMs), Molecular dynamics (MD), and Structure-activity relationship (SAR) models. The study explores the application of AI in biomedical fields, highlighting its enhanced predictive accuracy, treatment efficacy, diagnostic efficiency, faster decision-making, personalised treatment strategies, and precise medical interventions.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"717-748"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914960","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}
Journal of Drug TargetingPub Date : 2025-06-01Epub Date: 2025-01-08DOI: 10.1080/1061186X.2024.2449486
Arfa Nasrine, Sourav Mohanto, Soumya Narayana, Mohammed Gulzar Ahmed
{"title":"Enhanced pharmacokinetic approach for anastrozole via macromolecule-based silk fibroin nanoparticles incorporated <i>in situ</i> injectables for oestrogen-positive breast cancer therapy.","authors":"Arfa Nasrine, Sourav Mohanto, Soumya Narayana, Mohammed Gulzar Ahmed","doi":"10.1080/1061186X.2024.2449486","DOIUrl":"10.1080/1061186X.2024.2449486","url":null,"abstract":"<p><p>Breast cancer (BC) is a substantial reason for cancer-related mortality among women across the globe. Anastrozole (ANS) is an effective orally administered hormonal therapy for oestrogen-positive (ER+) BC treatment. However, several side effects and pharmacokinetic limitations restricted the uses of ANS in BC therapy. Therefore, this investigation developed an <i>in situ</i> gelling injectable-loaded silk fibroin (SF)-ANS NPs, which offers sustained drug release and improved pharmacokinetic properties compared to conventional oral formulations at the targeted site. The optimised <i>in situ</i> gel (ISG) incorporated SF-ANS-NPs were developed, and the pharmacokinetic parameters were accessed in subcutaneous administration of NMU-induced Wistar albino rats. The results demonstrated that SF-ANS-NP-ISG exhibited a significantly higher C<sub>max</sub>, T<sub>max</sub>, and AUC compared to pure ANS suspension. In addition, tumour multiplicity (1.40 ± 0.66), tumour latency (75 ± 9.2 days), and incidence rate (90 ± 2.1%) were recorded, and post-treatment analysis reported a marked reduction in tumour volume and weight compared to positive control within 90 days of a single dose. The SF-ANS-NP-ISG treated group's histopathological assessment indicated a low-grade carcinoma, reduced epithelial hyperplasia, and haemorrhage in mammary tumour tissues compared to positive control. Thus, the SF-ANS-NPs-ISG investigated to overcome the pharmacokinetic limitations of ANS further exhibited targeted delivery and bioavailability compared to conventional dosage forms.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"793-803"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927343","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":"Green synthesis of magnesium oxide nanoparticles using the extract of <i>Falcaria vulgaris</i> to enhance the healing of burn wounds.","authors":"Mozafar Khazaei, Mohammadali Meskaraf-Asadabadi, Fatemeh Khazaei, Sepide Kadivarian, Elham Ghanbari","doi":"10.1080/1061186X.2024.2445744","DOIUrl":"10.1080/1061186X.2024.2445744","url":null,"abstract":"<p><p>Treating burn lesions has always been challenging because any product should be cheap, accessible, and have anti-bacterial commodities and tissue regeneration properties. The green synthesis of magnesium oxide nanoparticles (GS-MgONPs) can create an optimal prospect that is safe with low toxicity in biological tissue and better safety for application while including the antibacterial effect. This recent study aimed to evaluate the effectiveness of burn wound treatment using GS-MgONPs in rats. GS-MgONPs were synthesised for the first time using a Falcaria vulgaris extract (FVE) and characterised. Thirty male Wistar rats were divided into five groups: An untreated group, conventional product treated group, GS-MgONPs (1 wt%), GS-MgONPs (3 wt%) and 5. FVE (1 wt%). Treatments commenced immediately following burn induction and were administered daily for a duration of 21 d. GS-MgONPs showed a spherical morphology with a diameter of less than 100 nm. The NPs (1% and 3 wt%) and FVE demonstrated significant growth inhibition against Staphylococcus aureus while showing no cytotoxic effects on human fibroblast cells. The proposed subjects treated with 1 wt% and 3 wt% GS-MgONPs were able to significantly increase the rate of wound closure (p < 0.05). Histological observations revealed that collagen formation and epithelial regeneration were more pronounced in the groups receiving 1 wt% and 3 wt% MgONPs. These results indicate that GS-MgONPs effectively enhance the regeneration process.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"761-772"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871230","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":"Review on anti-tumour lipid nano drug delivery systems of traditional Chinese medicine.","authors":"Ziwei Zhang, Rui Xiong, Qiyan Hu, Qiang Zhang, Shaozhen Wang, Yunyan Chen","doi":"10.1080/1061186X.2024.2448708","DOIUrl":"10.1080/1061186X.2024.2448708","url":null,"abstract":"<p><p>In recent years, the use of traditional Chinese medicine (TCM) in the treatment of cancer has received widespread attention. Treatment of tumours using TCM can effectively reduce the side effects of anti-tumour drugs, meanwhile to improve the treatment efficacy of patients. However, most of the active ingredients in TCM, such as saponins, alkaloids, flavonoids, volatile oils, etc., have defects such as low bioavailability and poor solubility in clinical application, which seriously restrict the application of TCM. Meanwhile, the encapsulation of TCM into lipid nano-delivery systems for cancer therapy has received much attention. Lipid nano-delivery systems are obtained by using phospholipids as the base material and adding other auxiliary materials under a certain preparation process, including, for example, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), microemulsions, and self-microemulsion drug delivery systems (SMEDDS), can resolve the application problems of TCM by improving the efficacy of active ingredients of TCM and reducing the toxicity of anti-tumour drugs. This paper focuses on the categories, development status, and research progress of lipid nano delivery system of TCM, aiming to provide a certain theoretical basis for further in-depth research and rational application of these systems.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"704-716"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914847","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}
Journal of Drug TargetingPub Date : 2025-06-01Epub Date: 2024-12-08DOI: 10.1080/1061186X.2024.2437440
Lissette Sanchez-Aranguren, Mohamad Anas Al Tahan, Muhammad Uppal, Parag Juvale, Mandeep Kaur Marwah
{"title":"Mitochondrial-targeted liposome-based drug delivery - therapeutic potential and challenges.","authors":"Lissette Sanchez-Aranguren, Mohamad Anas Al Tahan, Muhammad Uppal, Parag Juvale, Mandeep Kaur Marwah","doi":"10.1080/1061186X.2024.2437440","DOIUrl":"10.1080/1061186X.2024.2437440","url":null,"abstract":"<p><p>Liposomes, as nanocarriers for therapeutics, are a prominent focus in translational medicine. Given their biocompatibility, liposomes are suitable drug delivery systems rendering highly efficient therapeutic outcomes with minimal off-site toxicity. In different scenarios of human disease, it is essential not only to maintain therapeutic drug levels but also to target them to the appropriate intracellular compartment. Mitochondria regulate cellular signalling, calcium balance, and energy production, playing a crucial role in various human diseases. The notion of focusing on mitochondria for targeted drug delivery was proposed several decades ago, yet the practical application of this idea and its translation to clinical use is still in development. Mitochondrial-targeted liposomes offer an alternative to standard drug delivery systems, potentially reducing off-target interactions, side effects, and drug dosage or frequency. To advance this field, it is imperative to integrate various disciplines such as efficient chemical design, pharmacology, pharmaceutics, and cell biology. This review summarises scientific advances in the design, development and characterisation of novel liposome-based drug delivery systems targeting the mitochondria while revisiting their translational potential.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"575-586"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769220","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}