Maha Hamid Elhosany, Reham Mokhtar Aman, Ahmed M Awad, Germeen N S Girgis
{"title":"Melatonin loaded phytosomes for enhanced therapy against ethanol-induced gastric ulcer: formulation, optimization and <i>in vitro</i>/<i>in vivo</i> evaluation.","authors":"Maha Hamid Elhosany, Reham Mokhtar Aman, Ahmed M Awad, Germeen N S Girgis","doi":"10.1080/1061186X.2026.2746435","DOIUrl":"10.1080/1061186X.2026.2746435","url":null,"abstract":"<p><p>Healing of gastric ulcer (GU) can terminate the progression into more serious deteriorations. A promising and versatile vesicular nanoformulation, namely; phytosomes (PHY), was fabricated to maximise the GU healing efficacy of the naturally occurring bioactive component; melatonin (MLT). The solvent evaporation-hydration process ensnared MLT in the phytosomal complex, namely; melatonin loaded phytosomes (MLT-loaded PHY), that were fully described. A randomised full factorial design (2<sup>3</sup>) was applied with three independent key parameters (IKPs) at two levels. The optimal formulation, melatonin soybean phosphatidylcholine loaded chitosan coated phytosomes (MLT-SPC100 loaded/CS-coated PHY (F6)), was the most convenient one with acceptable MLT percentage entrapment efficiency (EE %, 69.467 ± 2.901%) and particle size (PS, 248.200 ± 03.830 nm) values, besides highest zeta potential (ZP, +30.267 ± 0.981 mV) one. Thereafter, it was further characterised with regard to its mucoadhesion efficiency, solid state characterisation, morphology, <i>in vitro</i> dissolution, physical stability, protein adsorption (opsonization) resistance, cytotoxicity, and finally <i>in vivo</i> healing efficacy against ethanol-induced GU in rats. Amongst the treated groups, the healing efficacy of the optimal formulation (F6) was noteworthy, as demonstrated by histological, immunohistochemical (IHC), and biochemical investigations. Hence, the aforementioned formulation deserves consideration as a promising GU remedial strategy.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-25"},"PeriodicalIF":4.7,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127680","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":"Correction.","authors":"","doi":"10.1080/1061186X.2026.2746177","DOIUrl":"https://doi.org/10.1080/1061186X.2026.2746177","url":null,"abstract":"","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-2"},"PeriodicalIF":4.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168936","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":"Hydrogel as Drug Delivery Systems for Bacteriophage Therapy: Overcoming Biological Barriers in Multidrug Resistant Bacterial Infections.","authors":"Mahsa Jalili, Mahmood Saffari, Farid Azizi Jalilian","doi":"10.1080/1061186X.2026.2746044","DOIUrl":"https://doi.org/10.1080/1061186X.2026.2746044","url":null,"abstract":"<p><p>The rapid emergence of multidrug-resistant (MDR) bacterial infections has intensified the demand for advanced antimicrobial drug delivery strategies capable of improving therapeutic efficacy while overcoming the limitations of conventional antibiotics. Bacteriophage therapy has re-emerged as a promising antibacterial approach because of its high specificity and potent activity against antibiotic-resistant pathogens. Nevertheless, the clinical translation of free bacteriophages remains restricted by multiple biological barriers, including rapid immune clearance, limited retention at infection sites, enzymatic degradation, poor stability, and inadequate penetration into bacterial biofilms. Hydrogel-based drug delivery systems have emerged as versatile biomaterial platforms that effectively address these challenges by protecting bacteriophages from environmental degradation, enabling localized administration, prolonging residence time, and providing sustained and controlled phage release. This review critically discusses the major biological barriers limiting successful bacteriophage therapy and highlights recent advances in hydrogel engineering strategies designed to improve phage encapsulation, stability, release behavior, and antibacterial efficacy. Furthermore, the physicochemical characteristics of hydrogels that influence phage delivery, including biocompatibility, porosity, swelling behavior, degradability, tissue adhesiveness, and mechanical properties, are examined in relation to their effects on phage retention and release. Recent applications of hydrogel-assisted bacteriophage delivery in chronic wound infections, biofilm-associated infections, surgical site infections, and other MDR bacterial diseases are summarized, with particular emphasis on localized antimicrobial therapy. Finally, current challenges related to formulation design, large-scale manufacturing, regulatory approval, and clinical translation are discussed, together with future perspectives for developing clinically applicable hydrogel-based phage delivery systems. Collectively, this review evaluates the current evidence supporting hydrogel-mediated bacteriophage delivery and identifies key considerations for the development and clinical translation of effective localized phage delivery systems against multidrug-resistant bacterial infections.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-77"},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147798","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}
Gajanan S Shinde, Himanshu Paliwal, Anil Kumar Singh, Anilkumar J Shinde, Sachin S Mali, Indrayani R Mohite, Asha S Jadhav, Vijay R Chidrawar, Sudarshan Singh, Bhupendra G Prajapati
{"title":"Hydrogel stabilised nanostructured lipid carrier fortified triamcinolone acetonide for the management of atopic dermatitis.","authors":"Gajanan S Shinde, Himanshu Paliwal, Anil Kumar Singh, Anilkumar J Shinde, Sachin S Mali, Indrayani R Mohite, Asha S Jadhav, Vijay R Chidrawar, Sudarshan Singh, Bhupendra G Prajapati","doi":"10.1080/1061186X.2026.2742499","DOIUrl":"10.1080/1061186X.2026.2742499","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a long-term skin disease that causes redness, itching, and a loss of skin barrier function, which sometime shows significant effect on a person's quality of life. In this study nanostructured lipid carrier (NLCs)-based hydrogel was fabricated for the topical delivery of triamcinolone acetonide (TA) with enhance therapeutic efficacy for the management of AD. TA-loaded NLCs were developed using high pressure homogeniser and characterised. The optimised NLCs composition showed a particle size of 92.06 nm, PDI of 0.324, ZP of -28.81 mV, and entrapment efficiency of 85.17%, suggesting good stability and drug incorporation. <i>Ex vivo</i> skin permeation studies of TA-NLCs hydrogel demonstrated sustained drug permeation of 79.86% at 8 h, significantly higher, compared to pure drug incorporated hydrogel (<i>p</i> < 0.05). Skin irritation studies verified the safety of the formulation with no significant signs of edoema and erythema. The anti-inflammatory effect was assessed using a carrageenan-induced rat paw edoema-based assay showed that the TA-NLCs hydrogel had higher inhibition of edoema than the marketed corticosteroid cream. Thus, the developed TA-NLCs hydrogel showed enhanced anti-inflammatory efficacy and sustained drug permeation, suggests that the developed TA-NLCs hydrogel could be an efficacious topical delivery system for the management of AD.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-18"},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110258","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}
Xinming Chen, Yanghui Xu, Xiao Han, Min He, Wen Zhou
{"title":"Targeting exosome conjugated with cardiac homing peptide alleviates myocardial infarction by delivering miRNAs.","authors":"Xinming Chen, Yanghui Xu, Xiao Han, Min He, Wen Zhou","doi":"10.1080/1061186X.2026.2687010","DOIUrl":"10.1080/1061186X.2026.2687010","url":null,"abstract":"<p><strong>Background: </strong>Conventional therapies for myocardial infarction (MI) have limited efficacy in restoring cardiac function. This study aimed to construct a novel engineered exosome platform for promoting post-MI cardiac regeneration and evaluate its therapeutic efficacy.</p><p><strong>Methods: </strong>CCK-8 assays, flow cytometry and western blotting were employed to evaluate the effects of DOPE-CHP-exosome on cardiomyocyte proliferation and apoptosis. The <i>in vivo</i> distribution of DOPE-CHP-exosome was assessed by fluorescence imaging, frozen sectioning and DiI tracing. Cardiac function was evaluated using echocardiography, Masson's trichrome staining and Sirius Red staining.</p><p><strong>Results: </strong>The novel DOPE-CHP-exosome functionalised with cardiac homing peptide (CHP) and loaded with miR-126, miR-145 or miR-340-5p (DOPE-CHP-miR) enhanced exosome uptake by cardiomyocytes, improved cell viability and reduced apoptosis in H<sub>2</sub>O<sub>2</sub>-induced primary cardiomyocyte injury models. <i>In vivo</i>, these exosomes markedly improved left ventricular contractility in MI mice, as evidenced by increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) and decreased left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). Additionally, the expression levels of CD31 and Ki67, markers of angiogenesis and proliferation, were significantly elevated. Notably, DOPE-CHP-miR-126 exhibited the most pronounced therapeutic effects.</p><p><strong>Conclusions: </strong>These DOPE-CHP-exosome alleviate MI and improve cardiac function by promoting cardiomyocyte viability and angiogenesis while inhibiting apoptosis.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030741","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":"Plant-derived bioactives and nanotechnology-enabled delivery in diabetic neuropathy: molecular mechanisms, therapeutic advances, and translational perspectives.","authors":"Karan Kumar Das, Biplab Debnath, Saikat Sen","doi":"10.1080/1061186X.2026.2741698","DOIUrl":"10.1080/1061186X.2026.2741698","url":null,"abstract":"<p><p>Diabetic neuropathy (DN), a long-term and progressive complication of diabetes mellitus, impairs approximated half of patients with diabetes and affects the quality of life considerably because of pain, sensory deficiency, and motor deficits. Traditional treatment including anticonvulsants, antidepressants, and opioids derived agents has provided some non-specific symptomatic benefit without aiming at the underlying causes like oxidative stress, chronic inflammation, and mitochondrial dysfunction. Curcumin, resveratrol, quercetin, and ginsenosides are few of phytochemicals, that are multi-targeted and can be used as therapeutic agents in DN treatment due to their antioxidant, anti-inflammatory, neuroprotective, and anti-glycation properties. These molecules have the effect of modulating redox-sensitive pathways, like NF-KB, SIRT1 and Nrf2, improving mitochondrial activity, inhibiting pro-inflammatory cytokines (TNF-alpha, IL-6), and stimulating nerve regeneration through neurotrophic factors such as NGF and BDNF. Although they have a promising pharmacological profile, problems like low oral bioavailability, non-clinical standardisation, and regulatory concerns hinder their adoption to clinical applications. The review also addresses the importance of large-scale and randomised clinical trials to confirm efficacy and develop uniform dosing regimens.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-33"},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069627","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":"Overcoming cellular barriers with cell-penetrating peptides: functional roles of individual amino acids.","authors":"Rasaq Olajide Akinsola, Kumaran Narayanan","doi":"10.1080/1061186X.2026.2739602","DOIUrl":"10.1080/1061186X.2026.2739602","url":null,"abstract":"<p><p>The delivery efficiency of cell-penetrating peptides (CPPs) is much lower than that of other non-viral delivery systems, mainly because of cellular barriers such as the plasma membrane, endosomal acidification, cytosolic degradation, and nuclear entry. We focus on how the functional properties of individual amino acids help overcome cellular barriers, thereby improving biomolecular delivery, and we also discuss CPPs that have advanced to clinical trials and highlight their strengths. We discuss how the plasma membrane acts as a major extracellular barrier that regulates biomolecule entry into cells, a challenge that can be addressed with peptides containing functional groups, such as basic amino acids, and how, after internalisation, CPPs cross intercellular barriers, and how their ability to do so mainly depends on the specific amino acids making up the peptide. This includes analyzing how histidine helps with endosomal escape, and conversely, how the presence of a nuclear localisation signal increases the likelihood of CPPs entering the nucleus. Specific amino acid residues successfully tackle these cellular bottlenecks. Incorporating basic amino acids effectively regulates entry across the plasma membrane, histidine assists with endosomal escape after internalisation, and the presence of a nuclear localisation signal increases the likelihood of CPPs entering the nucleus. Overcoming these barriers depends heavily on the presence and position of specific amino acid residues within a CPP. Sequence optimisation and rational design enhance delivery efficiency, supporting the translational potential of advanced CPPs currently evaluated in clinical trials.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-12"},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical and therapeutic relevance of B7-H3 in sarcomas: molecular insights from a systematic review.","authors":"Nouran Alwisi, Mohammad Abdel Hamid, Dahab Ghith, Salam Alshare, Lujain Adham, Samiha Sami, Giridhara Rathnaiah Babu, Semir Vranić","doi":"10.1080/1061186X.2026.2738912","DOIUrl":"10.1080/1061186X.2026.2738912","url":null,"abstract":"<p><p>Sarcomas are a heterogeneous group of mesenchymal malignancies characterised by substantial morphological and molecular diversity. Despite advances in surgery and systemic therapies, outcomes remain poor, underscoring the need for novel biomarkers and targeted therapies. We systematically assessed B7-H3 status in sarcomas. Forty-six studies were included (25 preclinical, 13 clinical, and eight mixed studies), most of which focused on osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. B7-H3 expression varied considerably across sarcoma subtypes and according to detection and scoring methods. The available evidence implicated B7-H3 in oncogenic transcriptional programs, miR-124 downregulation, matrix metalloproteinase-mediated shedding, and signalling pathways including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and epithelial-mesenchymal transition. Emerging therapeutic strategies targeting B7-H3 included CAR T-cell therapies, antibody-drug conjugates, Fc-optimized antibodies, radiolabeled antibodies, and fluorescence-guided surgery. In clinical evidence, B7-H3 expression showed potential associations with disease progression and selected survival outcomes; however, findings were limited by heterogeneous methodologies and relatively sparse clinical data. B7-H3 represents a promising biomarker and therapeutic target in sarcomas, with substantial preclinical evidence supporting its biological and therapeutic relevance. However, standardised approaches to B7-H3 detection and scoring, together with well-designed prospective clinical studies, are needed to establish its prognostic and predictive value and determine the clinical efficacy of B7-H3-directed therapies.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-14"},"PeriodicalIF":4.7,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149061679","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":"Nanocarrier-based drug delivery systems for remodeling the melanoma tumor microenvironment.","authors":"Hanqi Wang, Yuchen Sun, Hanlin Wang, Wei Shen, Guangxuan Ren, Mingyu Wang","doi":"10.1080/1061186X.2026.2743182","DOIUrl":"https://doi.org/10.1080/1061186X.2026.2743182","url":null,"abstract":"<p><p>Melanoma remains a major therapeutic challenge in dermatologic oncology because of its aggressive nature and high mortality rate, with traditional therapeutic approaches exhibiting significant limitations in efficacy. Although nanodrug delivery systems (NDS) present a promising paradigm to overcome existing therapeutic bottlenecks, a substantial translational gap persists between intricate preclinical material engineering and successful clinical translation. Notably, strategies designed to target the tumour microenvironment (TME) have shown promising progress in the clinical management of melanoma. This review contextualises the latest breakthroughs in melanoma-targeted NDS, elucidating how advanced nanocarriers exploit physiological and metabolic imbalances within the TME to reverse local immunosuppression and actively remodel the antitumor niche. Building on this foundation, we critically evaluate the performance of major synthetic platforms, including lipidic, polymeric, and inorganic materials. We also assess emerging biological and biomimetic nanocarriers, specifically comparing their biocompatibility and drug-loading capacities. Furthermore, we summarise the current landscape of Phase I-III clinical trials of nanomedicine-based therapies for melanoma. This review proposes a translational framework for the rational development of next-generation melanoma nanotherapeutics.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-17"},"PeriodicalIF":4.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110261","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}