Journal of Drug Targeting最新文献

{"title":"Brain targeted polymeric micelles as drug carriers for ischaemic stroke treatment.","authors":"Zirui Zhao, Huijia Song, Mengge Qi, Yurong Liu, Yanchao Zhang, Shuo Li, Huimin Zhang, Yongjun Sun, Yanping Sun, Zibin Gao","doi":"10.1080/1061186X.2024.2417190","DOIUrl":"10.1080/1061186X.2024.2417190","url":null,"abstract":"<p><p>Ischaemic stroke is a central nervous system disease with high morbidity, recurrence and mortality rates. Thrombolytic and neuroprotective therapies are the main therapeutic strategies for ischaemic stroke, however, the poor delivery efficiency of thrombolytic and neuroprotective drugs to the brain limits their clinical application. So far, the development of nanomedicine has brought opportunities for the above challenges, which can not only realise the effective accumulation of drugs in the target site, but also improve the pharmacokinetic behaviour of the drugs. Among the most rapidly developing nanoparticles, micelles gradually emerging as an effective strategy for ischaemic stroke treatment due to their own unique advantages. This review provided an overview of targeted and response-release micelles based on the physicochemical properties of the ischaemic stroke microenvironment, summarised the targeting strategies for delivering micellar formulations to the thrombus, blood-brain barrier, and brain parenchyma, and finally described the potentials and challenges of polymeric micelles in the treatment of ischaemic stroke.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"232-248"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review on recent advancements in drug delivery via selenium nanoparticles.","authors":"Muhammad Ahsan Waqar","doi":"10.1080/1061186X.2024.2412142","DOIUrl":"10.1080/1061186X.2024.2412142","url":null,"abstract":"<p><p>Nanotechnology has significantly impacted drug discovery and development over the past three decades, offering novel insights and expanded treatment options. Key to this field is nanoparticles, ranging from 1 to 100 nanometres, with unique properties distinct from larger materials. Selenium nanoparticles (SeNPs) are particularly promising due to their low toxicity and selective cytotoxicity against cancer cells. They have shown efficacy in reducing various cancers types and mitigating conditions like diabetic nephropathy and neurological disorders, such as Alzheimer's disease. This review highlights SeNPs' role in enhancing drug delivery systems, improving the absorption of water-soluble compounds, proteins, peptides, vaccines, and other biological therapies. By modifying nanoparticle surfaces with targeting ligands, drug delivery can achieve precise site-specific delivery, increasing effectiveness. SeNPs can be synthesised through physical, chemical, and biological methods, each offering advantages in stability, size, and application potential. Additionally, SeNPs enhance immune responses and reduce oxidative stress, validating their role in biotherapy and nanomedicine. Their ability to target macrophages and regulate polarisation underscores their potential in antimicrobial therapies. Recent advancements, such as mannosylated SeNPs for targeted delivery, exemplify innovative nanotechnology applications in medicine. Overall, SeNPs represent a promising frontier in nanomedicine, offering new avenues for treating and managing various diseases.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"157-170"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400452","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":"Humanized recombinant immunotoxin targeting hCG demonstrates therapeutic potential for advanced stage difficult to treat cancers.","authors":"Kirti Nain, Kritika Sonar, Sibasis Sahoo, Jagdish C Gupta, Sonam Grover, Arockiasamy Arulandu, G P Talwar","doi":"10.1080/1061186X.2024.2416247","DOIUrl":"10.1080/1061186X.2024.2416247","url":null,"abstract":"<p><p>We report the development of an immunotherapeutic molecule, a <i>Humanized</i> immunotoxin, for treating hCG-expressing advanced-stage cancers. PiPP, a high-affinity anti-hCG monoclonal antibody, is used in the immunotoxin for 'homing' hCG-positive cancer cells. The deimmunized (DI) form of α-Sarcin, a fungal-origin toxin that lacks functional T-cell epitopes, is used in the design to ensure minimal immunogenicity of the immunotoxin for repetitive use in humans. A single-chain variable fragment (scFv) of PiPP was constructed by linking the Humanized VH and VL regions of the antibody. The scFv part of the antibody was further linked to the toxin α-Sarcin (DI) at the gene level and expressed as a recombinant protein in <i>E. coli</i>. The immunotoxin was purified from the bacterial cell lysate and analysed for binding and cytotoxicity to hCG-secreting colorectal and pancreatic cancer cells. The results showed that the scFv(PiPP)-Sarcin immunotoxin was able to bind to colorectal and pancreatic cancer cells and killed approximately 85% of the cells. <i>In vivo</i> testing of the immunotoxin produced results similar to those of <i>in vitro</i> testing against colorectal adenocarcinoma-induced tumours. This immunotoxin could be a promising immunotherapeutic agent for treating colorectal, pancreatic and other terminal-stage hCG-expressing cancers.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"281-294"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467065","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 non-viral targeted RNA delivery vehicles - a key factor in success of therapeutic RNA.","authors":"Muhammad Waqas Choudry, Rabia Riaz, Muhammad Hassan Raza, Pashma Nawaz, Bilal Ahmad, Neelam Jahan, Shazia Rafique, Samia Afzal, Iram Amin, Muhammad Shahid","doi":"10.1080/1061186X.2024.2416241","DOIUrl":"10.1080/1061186X.2024.2416241","url":null,"abstract":"<p><p>Decade-long efforts in medicinal biotechnology have enabled large-scale in-vitro production of optimised therapeutic RNA constructs for stable in-vivo delivery and modify the expression of disease-related genes. The success of lipid nanoparticle-formulated mRNA vaccines against Severe acute respiratory syndrome Coronavirus-2 (SARS-Cov2) has opened a new era of RNA therapeutics and non-viral drug delivery systems. The major limiting factor in the clinical translation of RNA-based drugs is the availability of suitable delivery vehicles that can protect RNA payloads from degradation, offer controlled release, and pose minimal inherent toxicity. Unwanted immune response, payload size constraints, genome integration, and non-specific tissue targeting limit the application of conventional viral drug-delivery vehicles. This review summarises current research on nano-sized drug carriers, including lipid nanoparticles, polymer-based formulations, cationic nanoemulsion, and cell-penetrating peptides, for targeted therapeutic RNA delivery. Further, this paper highlights the biomimetic approaches (i.e. mimicking naturally occurring bio-compositions, molecular designs, and systems), including virus-like particles (VLPs), exosomes, and selective endogenous eNcapsidation (SEND) technology being explored as safer and more efficient alternatives.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"171-184"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400453","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":"Emerging advances in nano-biomaterial assisted amyloid beta chimeric antigen receptor macrophages (CAR-M) therapy: reducing plaque burden in Alzheimer's disease.","authors":"Nishabh Kushwaha, Drishti Panjwani, Shruti Patel, Priyanka Ahlawat, Mange Ram Yadav, Asha S Patel","doi":"10.1080/1061186X.2024.2417012","DOIUrl":"10.1080/1061186X.2024.2417012","url":null,"abstract":"<p><p>Alzheimer's disease is the most common form, accounting for 60-70% of 55 million dementia cases. Even though the precise pathophysiology of AD is not completely understood, clinical trials focused on antibodies targeting aggregated forms of β amyloid (Aβ) have demonstrated that reducing amyloid plaques can arrest cognitive decline in patients in the early stages of AD. In this study, we provide an overview of current research and innovations for controlled release from nano-biomaterial-assisted chimeric antigen receptor macrophage (CAR-M) therapeutic strategies targeted at AD. Nano-bio materials, such as iron-oxide nanoparticles (IONPs), can be made selectively (Hp-Hb/mannose) to bind and take up Aβ plaques like CAR-M cells. By using nano-bio materials, both the delivery and stability of CAR-M cells in brain tissue can be improved to overcome the barriers of the BBB and enhance therapeutic effects. By enhancing the targeting capabilities and stability of CAR-M cells, mRNA-loaded nano-biomaterials can significantly improve the efficacy of immunotherapy for plaque reduction in AD. This novel strategy holds promise for translating preclinical successes into clinical applications, potentially revolutionising the management of AD.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"185-205"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467064","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":"Methotrexate-Loaded solid lipid nanoparticles enhance the viability of cutaneous flaps: potential for surgical wound healing.","authors":"Cristina Pires Camargo, Maria Carolina Guido, Elaine Rufo Tavares, Priscila Oliveira Carvalho, Rolf Gemperli, Raul Cavalcante Maranhão","doi":"10.1080/1061186X.2024.2409884","DOIUrl":"10.1080/1061186X.2024.2409884","url":null,"abstract":"<p><p>Skin flaps are employed to cover cutaneous denuded surfaces, but ensuing flap necrosis often occurs. Previously, rats with myocardial infarction treated with lipid-core nanoparticles (LDE) loaded with methotrexate (MTX) improved myocardial irrigation and reduced necrosis. Here, the aim was to investigate the efficacy of LDE-MTX to preserve the viability of cutaneous flaps and its implications for surgical wound healing. Twenty-eight male rats were divided into 4 groups: (1) LDE, injected intraperitoneally with LDE only; (2) MTX (1 mg/Kg commercial MTX): (3) LDE-MTX (1 mg/Kg MTX associated with LDE), and controls without treatment. LDE, MTX or LDE-MTX were repeated after 2 days. Then, flap surgery (9x3cm) was performed on the dorsal region. Injections were continued every other day until day 7 when animals were euthanized. LDE-MTX treatment improved the total viable area of the flaps with a fourfold increase in blood flow and reduced inflammatory cell number (<i>p</i> < 0.001), accompanied by decreased protein expression of pro-inflammatory factors. SOD-1 was higher in LDE-MTX-treated rats (<i>p</i> < 0.05). In conclusion, LDE-MTX treatment achieved total viability of cutaneous flaps, with increased irrigation and diminished local inflammation. LDE-MTX may offer efficient and cost-effective prevention of cutaneous flaps and treatment for wounds from surgical procedures to be tested in future clinical studies.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"259-267"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501612","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":"Anti-angiogenic activity of polymeric nanoparticles loaded with ursolic acid.","authors":"Thomas Toshio Inoue, Vinicius Viana Pereira, Grasiely Faria de Sousa, Lays Fernanda Nunes Dourado, Armando da Silva Cunha-Junior","doi":"10.1080/1061186X.2024.2409881","DOIUrl":"10.1080/1061186X.2024.2409881","url":null,"abstract":"<p><p>Ursolic acid (UA) is an abundant natural product and has shown great promise for treating diseases related to the appearance of new blood vessels. However, its clinical use is limited due to its low solubility in aqueous media, resulting in reduced bioavailability. The present study aimed to synthetize poly(lactic-co-glycolic acid) nanoparticles loaded with UA by nanoprecipitation method and to evaluate the toxicity and anti-angiogenic activity using the <i>in vivo</i> chorioallantoic model. The nanoparticles were obtained in the size range that varied from 103.0 to 169.3 nm, they presented a uniform distribution (polydispersity index <0.2), and a negatively charged surface, with an encapsulation efficiency close to 50%. The release profile of the developed nanoformulation showed an initial burst in the first 2 h and demonstrated no acute toxicity (irritation index <0.9). Moreover, the chorioallantoic assay showed a significant reduction in both geometrical and topological parameters compared to saline control (<i>p</i> < .05). In conclusion, the study revealed a quick and simple way to obtain poly(lactic-co-glycolic) acid nanoparticles, a drug delivery system to UA, which showed potential antiangiogenic action and can be used to treat diseases involving neovascularisation.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"249-258"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review on endoplasmic reticulum-dependent anti-breast cancer activity of herbal drugs: possible challenges and opportunities.","authors":"Mayank Kumar Choudhary, Bhaskaranand Pancholi, Manoj Kumar, Raja Babu, Debapriya Garabadu","doi":"10.1080/1061186X.2024.2417189","DOIUrl":"10.1080/1061186X.2024.2417189","url":null,"abstract":"<p><p>Breast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The accumulation of misfolded proteins and subsequent activation of unfolded protein response (UPR) alters the homeostasis of endoplasmic reticulum (ER) lumen that ultimately causes oxidative stress in ER. The UPR activates stress-detecting proteins such as IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. The ER stress-dependent antitumor activity could be achieved either through suppressing the adaptive UPR to make cells susceptible to ER stress or by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Several herbal drugs trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of fifty-two herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC.Breast cancer (BC) is a major cause of cancer-related mortality across the globe and is especially highly prevalent in females. Based on the poor outcomes and several limitations of present management approaches in BC, there is an urgent need to focus and explore an alternate target and possible drug candidates against the target in the management of BC. The accumulation of misfolded proteins and subsequent activation of unfolded protein response (UPR) alters the homeostasis of endoplasmic reticulum (ER) lumen that ultimately causes oxidative stress in ER. The UPR activates stress-detecting proteins such as IRE1α, PERK, and ATF6, these proteins sometimes may lead to the activation of pro-apoptotic signaling pathways in cancerous cells. The ER stress-dependent antitumor activity could be achieved either through suppressing the adaptive UPR to make cells susceptible to ER stress or by causing chronic ER stress that may lead to triggering of pro-apoptotic signaling pathways. Several herbal drugs trigger ER-dependent apoptosis in BC cells. Therefore, this review discussed the role of fifty-two herbal drugs and their active constituents, focusing on disrupting the balance of the ER within cancer cells. Further, several challenges and opportunities have also been discussed in ER-dependent management in BC.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"206-231"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467062","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":"Exploring the potential of ferulic acid-loaded nanostructured lipid carriers: angiotensin inhibition via docking, formulation and pharmacokinetic and pharmacodynamics studies.","authors":"Preeti Rajabhau Meshram, Nisharani Sudhakar Ranpise","doi":"10.1080/1061186X.2025.2453743","DOIUrl":"10.1080/1061186X.2025.2453743","url":null,"abstract":"<p><p>Ferulic acid (FA) is a natural phenolic compound that has been documented for its antioxidant properties and potential in managing hypertension. However, its use is limited due to poor solubility and permeability (BCS Class IV classification). To overcome this, nanostructured lipid carriers (NLCs) of FA were developed using the emulsification probe sonication technique, with formulation optimized through Box-Behnken design. The optimized FA-NLCs (F12) demonstrated a particle size of 103.4 nm, zeta potential of -43.6 mV, polydispersity index of 0.531, and entrapment efficiency of 88.9%. Key Findings of the research manifested, that during <i>in-vitro</i> release studies, FA-NLCs showed sustained release action (40.34% over 24 h) compared to plain FA (103.13% in 4 h). Pharmacokinetics of FA-NLC suggested that increased C_max by 2.6-fold, AUC by 1.9-fold, and half-life significantly (p < .001), also Pharmacodynamics revealed that FA-NLCs reduced blood pressure more effectively (39.9 mmHg vs. 30.8 mmHg for plain FA; p < .001). Furthermore, FA-NLC was showing successful intestinal uptake through lymphatic absorption via clathrin-mediated endocytosis, bypassing first-pass metabolism, hence showed enhancement in bioavailability, Thus the study concluded that FA-NLCs significantly improve therapeutic efficacy and sustained blood pressure reduction compared to plain FA.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-23"},"PeriodicalIF":4.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971053","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":"Formulation, optimisation, and evaluation of Lornoxicam-loaded Novasomes for targeted ulcerative colitis therapy: in vitro and in vivo investigations.","authors":"Asmaa Badawy Darwish, Abeer Salama, Inas Essam Ibrahim Al-Samadi","doi":"10.1080/1061186X.2025.2456929","DOIUrl":"10.1080/1061186X.2025.2456929","url":null,"abstract":"<p><p>The purpose of this work was to create and assess Lornoxicam (LOR) loaded Novasomes (Novas) for the efficient treatment of ulcerative colitis. The study was performed using a 2³ factorial design to investigate the impact of several formulation variables. Three separate parameters were investigated: Surface Active agent (SAA) type (<i>X₁</i>), LOR concentration (<i>X₂</i>), and SAA: Oleic acid ratio (<i>X₃</i>). The dependent responses included encapsulation efficiency (<i>Y₁</i>: EE %), particle size (<i>Y₂</i>: PS), zeta potential (<i>Y₃</i>: ZP), and polydispersity index (<i>Y₄</i>: PDI). The vesicles demonstrated remarkable LOR encapsulation efficiency, ranging from 81.32 ± 3.24 to 98.64 ± 0.99%. The vesicle sizes ranged from 329 ± 9.88 to 583.4 ± 9.04 nm with high negative zeta potential values. The release pattern for Novas' LOR was biphasic and adhered to Higuchi's model. An in-vivo study assessed how LOR-Novas affected rats' acetic acid-induced ulcerative colitis (UC). The optimised LOR-Novas effectively reduced colonic ulceration (<i>p</i> < 0.05) and reduced the inflammatory pathway <i>via</i> inhibiting Toll-like receptor 4 (TLR4), Nuclear factor kappa β (NF-κβ) and inducible nitric oxide (iNO). At the same time, it elevated Silent information regulator-1(SIRT-1) and reduced glutathione (GSH) colon contents. Thus, the current study suggested that the formulation of LOR-Novas may be a viable treatment for ulcerative colitis.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":4.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006351","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}