Journal of Drug Targeting最新文献_第3页

Targeting lipopolysaccharides in gram-negative sepsis: therapeutic advances and challenges. 靶向脂多糖治疗革兰氏阴性脓毒症：治疗进展和挑战。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-10 DOI: 10.1080/1061186X.2025.2546487

Oluwakorede Akele, Freeha Rana, Sudeep Acharya, David LeDoux, Michel Chalhoub

{"title":"Targeting lipopolysaccharides in gram-negative sepsis: therapeutic advances and challenges.","authors":"Oluwakorede Akele, Freeha Rana, Sudeep Acharya, David LeDoux, Michel Chalhoub","doi":"10.1080/1061186X.2025.2546487","DOIUrl":"10.1080/1061186X.2025.2546487","url":null,"abstract":"Gram-negative bacterial sepsis remains a major global health threat, exacerbated by rising antimicrobial resistance and limited efficacy of current therapies. Central to its pathogenesis is lipopolysaccharide (LPS), a potent endotoxin that triggers overwhelming inflammation and organ dysfunction. This review critically evaluates emerging therapies targeting LPS in sepsis. Key strategies include antibiotics disrupting LPS biosynthesis and transport (e.g. zosurabalpin, darobactin), monoclonal and bispecific antibodies, extracorporeal endotoxin removal devices, and novel agents like LpxC inhibitors and nanotechnology-based platforms. Despite promising preclinical and early clinical data, translation to practice is limited by pharmacokinetic challenges, toxicity, resistance mechanisms, and inadequate patient stratification. Anti-LPS antibodies and polymyxins have shown selective benefits but face setbacks in broader trials. Nanotherapeutics and targeted filtration systems like oXiris® and Alteco® offer adjunctive potential but require validation through randomised studies. The complexity of LPS biology and sepsis heterogeneity demonstrates the need for precision medicine approaches and biomarker-guided interventions. Addressing scalability, regulatory hurdles, and cost-effectiveness will be critical to integrating LPS-targeted therapies into standard sepsis care. This review outlines a translational roadmap to harness these innovations and improve outcomes in Gram-negative sepsis.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-13"},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812030","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

Mannosylated chitosan-decorated PLGA nanoparticles for targeted pulmonary delivery of isoniazid: a promising approach in the treatment of tuberculosis. 甘露糖基化壳聚糖修饰的PLGA纳米颗粒靶向肺递送异烟肼：治疗结核病的一种有前途的方法。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-10 DOI: 10.1080/1061186X.2025.2554761

Riffat Maqbool, Dur E Nayab, Muhammad Mubeen, Hussain Ali, Salman Khan

{"title":"Mannosylated chitosan-decorated PLGA nanoparticles for targeted pulmonary delivery of isoniazid: a promising approach in the treatment of tuberculosis.","authors":"Riffat Maqbool, Dur E Nayab, Muhammad Mubeen, Hussain Ali, Salman Khan","doi":"10.1080/1061186X.2025.2554761","DOIUrl":"10.1080/1061186X.2025.2554761","url":null,"abstract":"Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), represents a significant challenge to global health. The management of the disease requires an extended course of antibiotic therapy, spanning a duration of 6 to 9 months. The complexity and duration of these regimens frequently lead to significant adverse effects, gastrointestinal issues, and the development of drug resistance. To address these challenges, the nanoparticulate based inhalable drug delivery system was designed as such by synthesising mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid (MC-PLGA-INH-PNPs) for targeted pulmonary delivery. Hence, nanoparticle based drug delivery system offers the potential to target and deliver the loaded drug directly into the M.tb infected cells. The prepared and optimised nano-formulation had a particle size of 154.9 ± 21 nm, zeta potential -23.2 ± 0.52 mV and entrapment efficiency of 79.8% ± 0.45. Additionally, the MC-PLGA-INH-PNPs exhibited a sustained drug release profile at physiological pH 7.4 for a period of 24 hr. An in vivo study of the MC-PLGA-INH-PNPs was performed on a mouse model utilising lipopolysaccharide as an inducer. The data obtained from the in vivo studies showed substantial improvements in lung tissues architecture and reduced inflammation. The group of animals treated with the MC-PLGA-INH-PNPs showed significant improvement in restoration of the disease when compared to pure drug treated group. These findings further indicate that these inhalable MC-PLGA-INH-PNPs hold a promising strategy for the treatment of tuberculosis and considerably improves pulmonary drug delivery to the target site. However, detailed investigations and testing of this nano-formulation on other relevant animal models will be essential to successfully translate this concept from laboratory to clinical practice.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956512","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

Bioengineered nanocomposite bacitracin zinc-loaded chitosan microspheres containing keratin/gelatine films for wound healing. 含角蛋白/明胶膜的细菌肽锌壳聚糖微球的生物工程纳米复合材料伤口愈合。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-05 DOI: 10.1080/1061186X.2025.2554758

Payal Shetty, Marina Koland, Suprit D Saoji, Mohammad Adnan Raza, Nilesh R Rarokar

{"title":"Bioengineered nanocomposite bacitracin zinc-loaded chitosan microspheres containing keratin/gelatine films for wound healing.","authors":"Payal Shetty, Marina Koland, Suprit D Saoji, Mohammad Adnan Raza, Nilesh R Rarokar","doi":"10.1080/1061186X.2025.2554758","DOIUrl":"10.1080/1061186X.2025.2554758","url":null,"abstract":"This study sought to create and characterize a novel antibiotic-loaded keratin-based film bandage for enhanced wound healing. Using the solvent casting method, keratin from chicken feathers was combined with gelatin (KG) in varying ratios to form films. Chitosan microspheres (Mc) were incorporated to achieve sustained release of bacitracin zinc (BZ). The microspheres were evaluated for particle size distribution, encapsulation efficiency, and in vitro drug release kinetics. The optimized film showed a controlled release profile with nearly 76% cumulative drug release over time. Embedding antibiotic-loaded microspheres within the keratin-gelatin matrix enabled prolonged delivery at the wound site, preventing infection and accelerating healing. In vivo excision wound studies demonstrated that the BZ-Mc-KG film achieved complete wound closure by day 20, significantly outperforming the disease control (p < .05). Comparative results indicated that microsphere-loaded gelatin films achieved 90% closure (p < .05), while free drug-loaded keratin-gelatin films reached 98% closure (p < .05). Slower healing was observed with drug-free keratin-gelatin films and standard mupirocin ointment (2.0% w/w). These findings highlight the synergistic potential of chicken feather keratin with BZ, supporting its application as a sustainable biomaterial for advanced wound dressings and effective therapeutic wound care strategies.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-18"},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956521","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

Chitosan-β-glycerophosphate thermogelling microneedles for transdermal contraceptive delivery of levonorgestrel. 壳聚糖-β-甘油磷酸酯热凝胶微针经皮给药左炔诺孕酮。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-05 DOI: 10.1080/1061186X.2025.2551816

Chethan Kumar K B, Sateesha S B, Ankith N A, Rajamma A J, Durgashree Diwakar, Girija E K, Likhitha C N

{"title":"Chitosan-β-glycerophosphate thermogelling microneedles for transdermal contraceptive delivery of levonorgestrel.","authors":"Chethan Kumar K B, Sateesha S B, Ankith N A, Rajamma A J, Durgashree Diwakar, Girija E K, Likhitha C N","doi":"10.1080/1061186X.2025.2551816","DOIUrl":"10.1080/1061186X.2025.2551816","url":null,"abstract":"This study presents the development of dissolving levonorgestrel-loaded microneedles (LMNs) incorporating a chitosan-β-glycerophosphate thermogelling system for sustained transdermal delivery of levonorgestrel (LNG) as a contraceptive. Polyvinylpyrrolidone K90 and Dextran 40 were included to enhance mechanical strength and controlled drug release. LMNs fabricated using poly dimethyl siloxane moulds exhibited uniform, sharp structures as confirmed by scanning electron microscopy. Fourier transform infra-red and X-ray diffraction analyses demonstrated chemical compatibility and physical stability of LNG within the matrix. The optimised LMNs showed significant mechanical strength (p < 0.05) and high insertion efficiency (F = 17.83, p = 3.03 × 10-8) across Parafilm® layers and fully dissolved within 30 min in porcine skin. Ex vivo studies revealed sustained LNG release (70.86% ± 0.42%) over 48 h, outperforming a topical gel (42.33% ± 0.91%). Drug release followed first-order kinetics (R2 = 0.996) and non-Fickian diffusion (n = 0.79), indicating a combined diffusion-erosion mechanism. In vivo evaluation in Wistar rats showed significant contraceptive efficacy, with reduced implantation sites (0.5 ± 0.55) and uterine thickness (3.66 ± 0.51 mm; p < 0.0001), comparable to oral LNG. These results highlight LMNs as a promising, minimally invasive platform for long-acting transdermal contraception, offering improved bioavailability, patient compliance and therapeutic effectiveness.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-13"},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956495","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

Effect of insulin aspart combined with insulin detemir and metformin on islet function in newly diagnosed type 2 diabetes mellitus. 分离胰岛素联合地特胰岛素及二甲双胍对新诊断2型糖尿病患者胰岛功能的影响。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-01 Epub Date: 2025-04-02 DOI: 10.1080/1061186X.2025.2477074

Hui Wang, Shang Li, Tianqi Zhao, Xixi Pan, Liangxue Wang

{"title":"Effect of insulin aspart combined with insulin detemir and metformin on islet function in newly diagnosed type 2 diabetes mellitus.","authors":"Hui Wang, Shang Li, Tianqi Zhao, Xixi Pan, Liangxue Wang","doi":"10.1080/1061186X.2025.2477074","DOIUrl":"10.1080/1061186X.2025.2477074","url":null,"abstract":"This trial evaluated the effects of insulin aspart (IAsp) and insulin detemir and metformin on islet function in newly diagnosed type 2 diabetes mellitus (T2DM). A total of 96 T2DM patients were randomised into the control group (insulin detemir + metformin treatment) and the study group (insulin detemir + metformin + IAsp treatment), with 48 cases each. The study compared clinical outcomes, as well as changes in fasting plasma glucose (FPG), 2-hour postprandial blood glucose (PBG), glycated haemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-β, quality of life, and sleep quality scores before and after treatment. Compared to the control group, the study group showed a higher total effective treatment rate, lower levels of FPG, 2-hour PBG, HbA1c, FINS, HOMA-IR, and sleep quality scores, while demonstrating higher HOMA-β and quality of life scores (all p < 0.05). Insulin detemir + metformin + IAsp was effective in treating T2DM, significantly enhancing insulin function and blood glucose levels, quality of life, and sleep quality. This combination therapy, though not commonly utilised in newly diagnosed T2DM patients, offers a novel therapeutic approach in clinical practice.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1394-1398"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573224","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

Recent progress in chitosan-based nanoparticles for drug delivery: a review on modifications and therapeutic potential. 壳聚糖基纳米药物递送材料的研究进展：修饰和治疗潜力综述。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-01 Epub Date: 2025-05-14 DOI: 10.1080/1061186X.2025.2502956

Kevser Bal, Sibel Küçükertuğrul Çelik, Sema Şentürk, Özlem Kaplan, Emine Büşra Eker, Mehmet Koray Gök

{"title":"Recent progress in chitosan-based nanoparticles for drug delivery: a review on modifications and therapeutic potential.","authors":"Kevser Bal, Sibel Küçükertuğrul Çelik, Sema Şentürk, Özlem Kaplan, Emine Büşra Eker, Mehmet Koray Gök","doi":"10.1080/1061186X.2025.2502956","DOIUrl":"10.1080/1061186X.2025.2502956","url":null,"abstract":"Chitosan, obtained from chitin by deacetylation, is a versatile biopolymer known for its biocompatibility, biodegradability and environmental friendliness. Combined with its chemical and physical modifiability, these properties have made chitosan an important material in biomedical and pharmaceutical fields, especially in drug delivery systems. Chitosan-based nanomaterials exhibit enhanced functions through various chemical modifications such as thiolation, acetylation, carboxylation and phosphorylation, as well as through physical and enzymatic approaches. These modifications address inherent limitations such as poor solubility, limited acid resistance and insufficient mechanical strength, expanding the applications of chitosan in tissue engineering, gene therapy, vaccine delivery, wound healing and bioimaging. This review provides an in-depth analysis of the chemical structure, physicochemical properties and modification strategies of chitosan. It also explores current methodologies for preparing chitosan nanoparticles, along with drug loading and release techniques. Various targeting strategies employed in chitosan-based delivery systems are examined in detail. To illustrate the clinical relevance of these approaches, representative examples from recent therapeutic studies are included. Moreover, it highlights future research directions and the innovation potential of chitosan-based materials.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1366-1393"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996797","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

Novel therapeutic approaches for non-small cell lung cancer: an updated view. 非小细胞肺癌的新治疗方法：最新观点。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-01 Epub Date: 2025-04-14 DOI: 10.1080/1061186X.2025.2489986

Niloufar Orooji, Shabnam Babaei, Manouchehr Fadaee, Hajar Abbasi-Kenarsari, Majid Eslami, Tohid Kazemi, Bahman Yousefi

{"title":"Novel therapeutic approaches for non-small cell lung cancer: an updated view.","authors":"Niloufar Orooji, Shabnam Babaei, Manouchehr Fadaee, Hajar Abbasi-Kenarsari, Majid Eslami, Tohid Kazemi, Bahman Yousefi","doi":"10.1080/1061186X.2025.2489986","DOIUrl":"10.1080/1061186X.2025.2489986","url":null,"abstract":"Non-small cell lung cancer (NSCLC) continues to be one of the leading causes of cancer-related mortality globally. Most patients who undergo surgical procedures may encounter distant metastasis or local recurrence, necessitating supplementary treatments such as radiation therapy, chemotherapy, or targeted therapy as adjuvant alternatives. Recent advancements in molecular biology and immunotherapy have paved the way for innovative therapeutic approaches that target specific genetic mutations and promote the immune response against tumour cells. This review explores emerging therapies, including targeted therapies such as tyrosine kinase inhibitors (TKIs) for actionable mutations (e.g., EGFR, ALK, ROS1), as well as the role of immune checkpoint inhibitors (ICIs) that employ the body's immune system to combat cancer. Additionally, we discuss the potential of exosome therapies, as well as promising nanotherapeutic options for the treatment of NSCLC. This study attempts to provide a thorough overview of the changing landscape of NSCLC treatment and its implications for enhancing patient outcomes by presenting these innovative techniques.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1306-1321"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788397","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

Strategies of overcoming osimertinib resistance in EGFR-mutated non-small cell lung cancer. egfr突变的非小细胞肺癌克服奥西替尼耐药的策略。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-01 DOI: 10.1080/1061186X.2025.2552431

Qiong Jiang, Yanxia Jin, Weidong Wang, Ying Chen, Leyi Tian, Xiaoyu Wang, Aobo Wu, Ruizhi Tian, Jicheng Pan, Yongsheng Gong

{"title":"Strategies of overcoming osimertinib resistance in EGFR-mutated non-small cell lung cancer.","authors":"Qiong Jiang, Yanxia Jin, Weidong Wang, Ying Chen, Leyi Tian, Xiaoyu Wang, Aobo Wu, Ruizhi Tian, Jicheng Pan, Yongsheng Gong","doi":"10.1080/1061186X.2025.2552431","DOIUrl":"https://doi.org/10.1080/1061186X.2025.2552431","url":null,"abstract":"Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has significantly advanced the treatment of non-small cell lung cancer (NSCLC), particularly in patients who develop resistance to first- and second-generation EGFR-TKIs. However, most patients inevitably develop resistance to the treatment, which presents a major challenge for long-term disease control. The molecular mechanisms underlying osimertinib resistance are complex and are generally categorised into EGFR-dependent and EGFR-independent pathways. To address this issue, various therapeutic strategies have been explored. These include the development of fourth-generation EGFR-TKIs, novel targeted agents and combination therapies involving molecular inhibitors, chemotherapeutic drugs, immunotherapeutic agents and gene inhibitors. In addition, nanomaterials, particularly selenium nanoparticles (SeNPs), have emerged as promising tools to overcome drug resistance. These nanomaterials can be used to enhance osimertinib delivery, improve its bioavailability, and modulate key resistance pathways at the cellular and molecular levels. This review comprehensively summarises the current understanding of resistance mechanisms to osimertinib and highlights cutting-edge therapeutic approaches. Special attention is given to nanotechnology-based strategies, which offer new possibilities for personalised and precise treatment of NSCLC. A deeper insight into these molecular mechanisms is essential for improving the clinical efficacy of osimertinib and prolonging the survival of patients with EGFR-mutant NSCLC.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956577","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

Design and formulation of fast-dissolving microneedles for the rapid transdermal delivery of lorazepam. 劳拉西泮快速透皮给药快溶微针的设计与制备。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-01 Epub Date: 2025-04-03 DOI: 10.1080/1061186X.2025.2483720

Punith M, Rajamma A J, Sateesha S B, Durgashree Diwakar, Girija E K, Chethan Kumar K B, Ankith N A, Mousam Bhowmik, Manjunatha P M

{"title":"Design and formulation of fast-dissolving microneedles for the rapid transdermal delivery of lorazepam.","authors":"Punith M, Rajamma A J, Sateesha S B, Durgashree Diwakar, Girija E K, Chethan Kumar K B, Ankith N A, Mousam Bhowmik, Manjunatha P M","doi":"10.1080/1061186X.2025.2483720","DOIUrl":"10.1080/1061186X.2025.2483720","url":null,"abstract":"This study investigates lorazepam-loaded dissolving microneedles (LMNs) as a fast-acting and minimally invasive treatment for status epilepticus. The LMNs were developed using a micro-moulding technique with an optimised combination of PVP K30, Dextran 40 and Pullulan. Their stability was confirmed through Fourier transform infra-red (FTIR) spectroscopy and X-ray diffraction (XRD) analysis. The Parafilm® membrane insertion test demonstrated 100% penetration efficiency, verifying their ability to effectively pierce the skin. Scanning electron microscopy (SEM) imaging revealed well-defined microneedles with precise dimensions (800 µm height, 200 µm base and 500 µm pitch). The LMNs rapidly dissolved in the subdermal layer of porcine skin. An ex vivo drug diffusion study showed that 3-5% of the encapsulated lorazepam was released within 30 min, with a cumulative release of 79.3% over 24 h. An acute dermal irritation study confirmed the biocompatibility and skin tolerance of the LMNs. Additionally, an in vivo anti-convulsant efficacy study in Albino Wistar rats subjected to maximal electroshock seizures demonstrated significant anticonvulsant effects (p < .05), confirming efficient systemic delivery of lorazepam. These findings highlight LMNs as a rapid-acting, non-invasive transdermal drug delivery system for managing status epilepticus, particularly in ambulatory care settings.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1399-1411"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710300","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

Engineered extracellular vesicle with RAGE-antagonist peptide for delivery of anti-miRNA155 oligonucleotides to inflammatory lung cells. rage -拮抗剂肽工程细胞外囊泡用于向炎性肺细胞递送抗mirna155寡核苷酸。

IF 3.9 4区医学

Journal of Drug Targeting Pub Date : 2025-09-01 Epub Date: 2025-05-07 DOI: 10.1080/1061186X.2025.2500040

Chuanyu Zhuang, Minji Kang, Jihun Oh, Chowon Lee, Minhyung Lee

{"title":"Engineered extracellular vesicle with RAGE-antagonist peptide for delivery of anti-miRNA155 oligonucleotides to inflammatory lung cells.","authors":"Chuanyu Zhuang, Minji Kang, Jihun Oh, Chowon Lee, Minhyung Lee","doi":"10.1080/1061186X.2025.2500040","DOIUrl":"10.1080/1061186X.2025.2500040","url":null,"abstract":"Acute lung injury (ALI) is an inflammatory lung disease. In lungs afflicted with ALI, microRNA-155 (miR-155) is over-expressed, inducing pro-inflammatory cytokines by inhibition of suppressor of cytokine signalling 1 (SOCS1). In addition, receptor for advanced glycation endproducts (RAGEs) are activated, facilitating the expression of pro-inflammatory cytokines. Therefore, anti-miRNA-155 oligonucleotides (AMO155) and a RAGE-antagonist peptide (RAP) have been suggested as effective therapeutics of ALI. In this study, extracellular vesicles (EVs) were developed as a carrier of AMO155 and the RAP for a combination therapy of ALI. RAP-engineered EVs (RAP-EVs) were produced by the expression of a recombinant RAP-Lamp2b fusion protein on the surface. Then, cholesterol-modified AMO155 (AMO155c) was loaded onto the RAP-EV. In vitro assays showed that the RAP-EV delivered AMO155c as efficiently as unmodified EV (Unmod-EV). For in vivo animal experiments, AMO155c-loaded EVs (AMO155c/EVs) were administrated into the ALI models by intratracheal instillation. The results showed that the AMO155c/RAP-EV induced SOCS1 and decreased RAGE expression more efficiently than the control systems. Compared to the controls, the inflammatory responses, such as pro-inflammatory cytokines, were effectively reduced by the AMO155c/RAP-EV. The results indicated that the RAP-EV could be an efficient carrier for the combination therapy of the RAP and AMO155c.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1462-1470"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967852","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