Current drug delivery最新文献

{"title":"Pharmacological and Therapeutic Roles of Wild Pistachio and Its Nanoformulations in Endocrine, Metabolic, and Other Diseases: A Comprehensive Review.","authors":"Hadis Ahmadirad, Irfan Ahmad, Mojgan Noroozi-Karimabad","doi":"10.2174/0115672018452820261006095941","DOIUrl":"https://doi.org/10.2174/0115672018452820261006095941","url":null,"abstract":"<p><strong>Introduction: </strong>Wild pistachio (Pistacia atlantica, P. atlantica) is a promising natural source of bioactive compounds, particularly polyphenols, that may help manage metabolic and endocrine disorders through its antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. Nanotechnology further offers opportunities to improve the stability, solubility, bioavailability, and targeted delivery of these compounds.</p><p><strong>Methods: </strong>This comprehensive review summarizes recent scientific literature on the phytochemical composition, nutritional value, pharmacological properties, and nanoformulation strategies associated with P. atlantica. Special attention was given to evidence relevant to metabolic syndrome, diabetes, obesity, and hormone-related disorders.</p><p><strong>Results: </strong>The reviewed studies indicate that P. atlantica contains biologically active compounds with the potential to reduce oxidative stress, inflammation, aging-related damage, and carcinogenic processes. Preclinical evidence suggests beneficial effects on metabolic and endocrine pathways, while nanoencapsulation and nanoliposome-based delivery systems may enhance the therapeutic performance of its bioactive constituents by improving stability and absorption.</p><p><strong>Discussion: </strong>Overall, the available evidence suggests that P. atlantica has considerable therapeutic potential, particularly when combined with nanoformulation approaches that may improve the stability, bioavailability, and delivery of its bioactive constituents. Nevertheless, most of the current evidence is derived from experimental studies, and differences in study design, formulations, and outcome measures make it difficult to draw firm clinical conclusions. Further well-designed translational and clinical research is needed before these findings can be confidently applied in practice.</p><p><strong>Conclusion: </strong>P. atlantica and its nanoformulations represent promising candidates for future supportive interventions in metabolic and endocrine diseases. However, the current evidence is largely preclinical, and further in vitro, in vivo, and clinical studies are needed to confirm efficacy, safety, and translational potential.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization, <i>In vitro</i> and <i>In vivo</i> Evaluation of an Azithromycin Nanosuspension-Based Nanogel for Enhanced Dermal Delivery.","authors":"Omar Saeb Salih, Nawar Mikhael Toma, Manar Adnan Tamer, Sajad Moneim Aljubouri, Shahbaa Mohammed Ati","doi":"10.2174/0115672018500887260930105834","DOIUrl":"https://doi.org/10.2174/0115672018500887260930105834","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Azithromycin is a BCS class II macrolide antibiotic characterized by poor aqueous solubility, a limited dissolution rate, and relatively low oral bioavailability (37%), limiting its therapeutic effectiveness for the treatment of skin infections. This study aimed to design and optimize an azithromycin nanosuspension-based nanogel using a Box-Behnken design.</p><p><strong>Methods: </strong>Azithromycin nanosuspension was prepared by the antisolvent precipitation method followed by probe sonication. The effects of formulation-variable concentrations on particle size, polydispersity index, and zeta potential were optimized using a Box-Behnken design. The optimized formulation was incorporated into a Carbopol-based gel and subsequently evaluated. In vitro release, ex vivo skin permeation, in vivo dermal irritation, antimicrobial activity, and stability studies were performed.</p><p><strong>Results: </strong>The optimized formulation contained PVP K30 (0.1% w/v), Tween 80 (0.2% w/v), and HPMC E5 (0.02% w/v), yielding a particle size of 30.65 ± 1.7 nm, polydispersity index of 0.13 ± 0.01, and zeta potential of -0.53 ± 0.13 mV. The nanogel significantly enhanced ex vivo permeation across rat skin (flux 16.8 ± 0.45 μg/cm²·min) compared with the plain hydroalcoholic gel (6.0 ± 0.2 μg/cm²·min). The optimized nanogel exhibited appreciable dermal safety and enhanced antibacterial efficacy against Staphylococcus aureus and Escherichia coli.</p><p><strong>Discussion: </strong>The improved performance of the selected nanogel was attributed to the nanosuspended particles, which enhanced azithromycin dissolution, localization at the application site, and permeation across the dermal layers.</p><p><strong>Conclusion: </strong>The optimized nanogel exhibited enhanced dissolution, controlled drug release, improved skin permeation, local antimicrobial efficacy, and good dermal tolerability.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanocarrier Systems for Nystatin Delivery: Formulation Performance and Therapeutic Implications in Candidiasis Treatment.","authors":"Evi Sulastri, Maya Nurul Rahma, Khaled M Elamin, Ahmed Fouad Abdelwahab Mohammed, Safwat A Mahmoud, Nasrul Wathoni","doi":"10.2174/0115672018493958261005052727","DOIUrl":"https://doi.org/10.2174/0115672018493958261005052727","url":null,"abstract":"<p><p>Nystatin is a commonly used antifungal medicine for the treatment of candidiasis, particularly in superficial and mucosal infections. Its clinical usefulness is limited by poor water solubility, instability, a short residence time in the mucosa, and low absorption. This review critically evaluates 22 eligible studies (PRISMA 2020-compliant search, January 2004-December 2025) on nano- and microparticulate delivery systems for nystatin in the treatment of candidiasis, using a novel analytical framework that maps nanocarrier physicochemical properties to site-specific delivery requirements across oral, cutaneous, and vulvovaginal candidiasis. Nanoemulsions, nanosuspensions, Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), polymeric nanoparticles, and vesicular systems, specifically liposomes and nanocubosomes, are evaluated by standardized physicochemical parameters, evidence-graded antifungal endpoints, and a translational readiness evaluation. Nanoemulsions and NLCs demonstrate the most favorable translational profiles. Challenges related to manufacturing scalability, long-term stability, and regulatory acceptance remain barriers to clinical translation.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Nanogels for Controlled Drug Release: A Review of Synthesis and Biomedical Integration.","authors":"Damini Yadav, Asha Raghav, Sujata Sujata, Poonam Vashisht, Parijat Pandey","doi":"10.2174/0115672018492081260929071418","DOIUrl":"https://doi.org/10.2174/0115672018492081260929071418","url":null,"abstract":"<p><strong>Introduction: </strong>Nanogels are broadly tuneable nanoparticles formulated for controlled drug delivery and represent an effective means of delivering active pharmaceutical compounds. This review aims to provide a broad understanding of nanogels by elucidating their fundamental properties, drug-release mechanisms, synthesis methods, patents, clinical trials and recent technological advancements. It further explores the underlying mechanisms that govern nanogels' functionality, as well as the significant challenges and persistent limitations associated with their biomedical use.</p><p><strong>Methods: </strong>A detailed analysis of the current literature was conducted to examine nanogels' fabrication techniques, physicochemical properties, and their expanded applications in drug delivery and disease modification. This review has also encompassed recent patents, clinical trial progress, and technological advancement related to nanogel-based drug delivery.</p><p><strong>Results: </strong>Some nanogels have been reported to exhibit high biocompatibility, strong water retention, and beneficial mechanical properties, making them an ideal system for drug delivery. Nanogels characterized by tunable size, large surface area, and a tangled internal network provide a diverse platform for advanced therapeutic applications.</p><p><strong>Discussion: </strong>Nanogel-based drug delivery shows growing translational interest, but a significant gap remains between laboratory innovation and clinical implementation. Nanogels offer promise for targeted and sustained drug delivery, but require optimized synthesis, mechanistic studies, robust preclinical evaluation, and interdisciplinary collaboration.</p><p><strong>Conclusion: </strong>Nanogels represent a promising, versatile drug delivery system with enormous potential for controlled, targeted applications. Advancements and mechanistic insights are essential to overcome current limitations. Future research should be deeply focused on enhancing their drug-delivery capabilities and expanding their clinical applications across a broad spectrum of diseases.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobots in Precision Medicine: Transforming Drug Delivery Systems.","authors":"Ritesh Sharma, Mohini Chaturvedi, Sonu Yadav, Mohd Sameer Khan, Abdullah Al Noman, Kuldeep Singh, Divya Jain, Jeetendra Kumar Gupta, Mukesh Chandra Sharma","doi":"10.2174/0115672018403495251210132701","DOIUrl":"https://doi.org/10.2174/0115672018403495251210132701","url":null,"abstract":"<p><p>Nanotechnology has emerged as a transformative force in modern healthcare, particularly through the innovative use of nanobots for drug delivery. These microscopic, programmable devices are designed to navigate biological systems and deliver therapeutic compounds directly to targeted tissues or cells, thereby enhancing drug bioavailability and minimizing systemic side effects. This review explores recent advancements in nanobot technology, including their engineering with advanced materials, magnetic control systems, and programmable designs that enable precise, adaptable drug delivery. The implications of nanobots are profound, offering targeted interventions in oncology, neurology, and infectious diseases, along with the potential for personalized medicine and real-time monitoring of treatment. Despite the promising outlook, significant challenges remain in optimizing biocompatibility, propulsion mechanisms, and regulatory frameworks. This work highlights the need for interdisciplinary collaboration to refine nanobots' clinical applications and unlock their full potential in shaping the future of targeted therapeutic approaches.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal Medicine in Episiotomy Wound Healing: A Systematic Review.","authors":"Mansoureh Refaei, Arezoo Shayan, Elham Fatholahi, Roya Ahmadinia Tabesh, Fahimeh Ezzati Arasteh, Azita Tiznobaik","doi":"10.2174/0115672018448913260923044628","DOIUrl":"https://doi.org/10.2174/0115672018448913260923044628","url":null,"abstract":"<p><strong>Introduction: </strong>Episiotomy is a common obstetric intervention following vaginal delivery and is frequently associated with pain, delayed wound healing, and postpartum discomfort. Inadequate healing of episiotomy wounds may result in infection, prolonged pain, and long-term perineal complications. Traditional and complementary medicine, particularly herbal therapies, has been increasingly investigated as a potential strategy to enhance wound healing and reduce pain after episiotomy. This systematic review aimed to evaluate the effects of herbal medicines on episiotomy wound healing and pain reduction.</p><p><strong>Methods: </strong>This systematic review was conducted in accordance with PRISMA guidelines. Electronic databases including PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for interventional studies published between 2000 and November 21, 2024. Eligible studies were clinical trials evaluating the effects of herbal medicines on episiotomy wound healing and/or pain outcomes among postpartum women. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklist.</p><p><strong>Results: </strong>Of 304 identified records, 73 studies met the inclusion criteria. Most studies were randomized or quasi-experimental trials conducted among primiparous women. Herbal interventions including Aloe vera gel, lavender oil, olive oil, green tea extract, yarrow ointment, chamomile cream, and Hypericum perforatum were the most frequently investigated. The majority of studies reported significant improvements in wound healing scores and/or reductions in pain intensity compared with placebo, routine care, or conventional treatments. Based on the JBI critical appraisal assessment of the 73 included studies, 51 studies (69.9%) were classified as high quality, 21 (28.8%) were classified as moderate quality, and one study (1.4%) was classified as low quality.</p><p><strong>Discussion: </strong>Overall, the findings suggest that several herbal medicines-particularly Aloe vera, lavender, and olive oil-may accelerate episiotomy wound healing and alleviate pain. However, heterogeneity in study design, intervention formulations, and outcome measures limits direct comparison across studies.</p><p><strong>Conclusion: </strong>Herbal medicines appear to be promising complementary interventions for episiotomy wound management. Nevertheless, further high-quality, multicenter randomized controlled trials with standardized protocols and long-term follow-up are required to confirm their efficacy and safety.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Laboratory to Clinic: Translational Challenges, Lessons, and Future Strategies for microRNA Delivery Systems.","authors":"Qianqian Liu, Liwei Jia, Xin Meng, Baoyue Xu, Yu Zhong, Yanhua Zhu","doi":"10.2174/0115672018510883260914050642","DOIUrl":"https://doi.org/10.2174/0115672018510883260914050642","url":null,"abstract":"<p><p>MicroRNA (miRNA)-based therapeutics can modulate disease-associated gene networks by restoring protective miRNAs or inhibiting pathogenic miRNAs, yet clinical translation remains limited despite substantial preclinical progress. This review critically evaluates representative clinical and advanced translational programs, including Miravirsen, MRX34, Cobomarsen, Remlarsen, RGLS4326, and farabursen (RGLS8429), to compare molecular designs, delivery approaches, development outcomes, and translational bottlenecks. These programs show that clinical success cannot be explained by delivery efficiency alone, but depends on the interplay among tissue selectivity, intracellular delivery and endosomal escape, immune compatibility, sequence- and network-level pharmacology, PK/PD, and Chemistry, Manufacturing, and Controls (CMC). We also assess emerging strategies, including organ-selective lipid nanoparticles, stimuli-responsive nanocarriers, extracellularvesicle- based systems, and local delivery, with emphasis on their translational potential and remaining validation needs. Drawing on these lessons, we propose a Four-Pillar Framework integrating Delivery Systems, Immune Safety, CMC and Manufacturing Readiness, and biomarker-guided Clinical Design. Together, these principles support coordinated optimization across biological, pharmaceutical, and clinical dimensions rather than isolated improvement of individual delivery parameters.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Principles of Extracellular Vesicles for Central Nervous System Therapies.","authors":"Nate Roy, Dariusz Zurawek, Gustavo Turecki","doi":"10.2174/0115672018485352260907113702","DOIUrl":"https://doi.org/10.2174/0115672018485352260907113702","url":null,"abstract":"<p><p>Extracellular Vesicles (EVs) are active mediators of intercellular signaling in the Central Nervous System (CNS), operating alongside synaptic transmission as an extra form of wireless communication between neurons and other brain cell types. Their biocompatibility positions them as promising carriers for neurobiological therapeutics; however, translation hinges on clarifying when and how EVs traverse the Blood-Brain Barrier (BBB) and how their design can be aligned to pathophysiology. We synthesize evidence for BBB transport from in vitro models and in vivo visualization and functional studies and build on this foundation by outlining engineering strategies for CNS tropism both to the brain and within it. Across these areas, current advances remain largely siloed despite clear mechanistic interdependence, underscoring the need for standardized frameworks that integrate barrier biology, engineering design, and disease context. We argue that progress now depends on two fronts: developing preclinical models that accurately capture mechanisms governing bidirectional EV transport through the BBB and aligning vesicle design and delivery parameters with those mechanisms. Achieving this will require closer integration with biomarker discovery and greater standardization across preclinical workflows. Together, these steps chart a path from proof of concept to clinically adaptable EV therapeutics for CNS disease.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Protein-Based Polymers as Nanocarriers for Drug Delivery.","authors":"Auwal Ibrahim Tanko, Md Rashedul Islam, Muhammad Afzal, Misbahuddin Rafeeq, Hussam Aly Sayed Murad, Sami I Alzarea, Rabeea Mustafa Ali Daoub, Hisham N Altayb, Muhammad Shahid Nadeem, Imran Kazmi","doi":"10.2174/0115672018496503260910072814","DOIUrl":"https://doi.org/10.2174/0115672018496503260910072814","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Protein-based polymeric nanocarriers are increasingly being investigated as biodegradable, biocompatible systems for drug and gene delivery. This review critically examines major protein-based polymeric nanocarriers and globular proteins, including casein, gelatin, gliadin, collagen, elastin, albumin, silk fibroin, lectins, legumin, ferritin, zein, virus-like particles, silk-like polypeptides, elastin-like polypeptides, and silk-elastin-like protein polymers.</p><p><strong>Methods: </strong>Relevant studies were identified from major scientific databases using search terms related to protein-based polymeric nanocarriers, drug delivery, protein nanoparticle, recombinant protein polymer, ferritin nanocages, and virus-like particles. Studies were considered if they discussed carrier design, formulation methods, physicochemical characterization, biological performance, clinical translation, patents, or recent developments in protein-based delivery systems.</p><p><strong>Results: </strong>Protein-based polymeric nanocarriers can be classified into five main structural classes: protein nanoparticles, protein micelles, protein nanocages, recombinant protein polymer assemblies, and protein-drug conjugate or fusion systems. Albumin-based nanoparticles remain the most clinically advanced platform, whereas ferritin nanocages and virus-like particles provide structurally defined systems for receptor-mediated targeting. Plant-derived proteins such as casein, zein, and gliadin form polymeric matrices relevant for oral delivery, whereas silk fibroin, collagen, gelatin, and recombinant protein polymers self-assemble into structures that support sustained, local, and stimulus-responsive delivery.</p><p><strong>Discussion: </strong>Despite their potential, protein-based polymeric nanocarriers face several challenges, including protein corona formation, immunogenicity, storage instability, batch variability, scale-up limitations, and regulatory uncertainty.</p><p><strong>Conclusion: </strong>Future development should prioritize reproducible manufacturing, safer surface modification, improved stability, and rigorous evaluation of immune responses and translational feasibility.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Novel Drug Delivery Systems for Targeting the Brain: Overcoming Barriers and Enhancing Therapeutic Efficacy.","authors":"Manish R Bhise, K Thejomoorthy, Mohit Kumar, Paresh Kumar N Patel, Vishakha Mahajan, Kamran Javed Naquvi, Israr Ansari, Ajay Kumar","doi":"10.2174/0115672018474663260907142216","DOIUrl":"https://doi.org/10.2174/0115672018474663260907142216","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is critical in CNS pharmacotherapy; it blocks the entry of 98 per cent of small-molecule compounds and almost all macromolecules into the brain parenchyma via tight junction complexes, efflux transporter action, and enzymatic breakdown. This review focuses on the mechanistic basis of BBB resistance and analyses the current landscape of new drug delivery systems developed to overcome this barrier. We elaborate on polymeric nanocarriers, lipid-based nanocarriers, exosomes, dendrimers, and metallic nanoparticles, including surface engineering, the possibility of receptor-mediated transcytosis via transferrin, LRP1, and glucose transporter receptors, and known preclinical efficacy in glioblastoma, Alzheimer's disease, and Parkinson's disease. Non-invasive delivery through the nose is evaluated as intranasal delivery because it utilises olfactory and trigeminal receptors to circumvent systemic delivery. BBB modulation mediated by focused ultrasound is mentioned as one of the physical adjuncts to enhance CNS penetration. Clinical translation is poor, even where the preclinical data are positive. Most late-stage failures can be attributed to protein corona formation, anti-PEG immunogenicity, interpatient heterogeneity in the BBB, and manufacturing scalability. These obstacles are critically evaluated with the help of recent clinical trial evidence, where preclinical models cannot be used as predictors of human outcomes. In the future, AI-based nanocarrier design, machine-learning-driven prediction of BBB permeability, and patient-centred nanomedicine platforms will provide a viable pathway to customised CNS therapeutic approaches. Multimodal strategies integrating RMT, stimuli-responsive carriers, and CRISPRbased gene delivery may collectively overcome the translational gap that single-platform approaches have consistently failed to bridge.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}