Pharmaceutics最新文献

{"title":"Expression of Concern: Montenegro et al. Resveratrol-Loaded Lipid Nanocarriers: Correlation Between In Vitro Occlusion Factor and In Vivo Skin Hydrating Effect. <i>Pharmaceutics</i> 2017, <i>9</i>, 58.","authors":"Pharmaceutics Editorial Office","doi":"10.3390/pharmaceutics18101331","DOIUrl":"https://doi.org/10.3390/pharmaceutics18101331","url":null,"abstract":"<p><p>With this notice, the <i>Pharmaceutics</i> Editorial Office alerts readers to concerns regarding this article [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Mehenni et al. Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B. <i>Pharmaceutics</i> 2018, <i>10</i>, 235.","authors":"Lyes Mehenni, Malika Lahiani-Skiba, Guy Ladam, François Hallouard, Mohamed Skiba","doi":"10.3390/pharmaceutics18101283","DOIUrl":"10.3390/pharmaceutics18101283","url":null,"abstract":"<p><p>The journal retracts the article titled \"Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B\" [...].</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 10","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Angelica dahurica</i> Exosome-like Nanovesicles Delivered by Ultrasonic Nebulization Alleviate Allergic Rhinitis and Modulate NF-κB Signaling.","authors":"Anqi Zhou, Xiao Li, Lin Zhao, Song Zhang, Xiaowei Li, Qiulin Yue, Xin Sun, Kai Zheng, Le Su","doi":"10.3390/pharmaceutics18091193","DOIUrl":"10.3390/pharmaceutics18091193","url":null,"abstract":"<p><p><b>Background:</b> Current treatments for allergic rhinitis (AR) are associated with side effects and do not provide a definitive cure. <i>Angelica dahurica</i> has recognized anti-inflammatory activity; however, the therapeutic potential of <i>Angelica dahurica</i>-derived exosome-like nanovesicles (ADELNs) in AR remains insufficiently explored. In addition, although ultrasonic nebulization is widely used for airway inflammatory diseases, including pulmonary disorders and asthma, its application in AR has received limited attention. <b>Methods:</b> ADELNs were isolated by differential centrifugation and ultracentrifugation and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), thin-layer chromatography (TLC), SDS-PAGE, and agarose gel electrophoresis. To evaluate the effects of ultrasonic nebulized ADELNs on AR, we designed and validated a mouse nasal nebulization device. Cellular inflammation and OVA-induced AR mouse models were then established, and inflammatory and pathological indicators were assessed using ELISA, RT-qPCR, histological staining, and related assays. Western blotting was used to investigate the involvement of the NF-κB signaling pathway. <b>Result:</b> ADELNs were successfully isolated and exhibited typical exosome-like characteristics. The ultrasonic nebulization device showed good stability. Nebulized ADELNs alleviated AR symptoms in mice in a concentration-dependent manner, reduced inflammatory cytokines, serum histamine, and OVA-specific IgE, downregulated inflammatory cytokine mRNA expression in the nasal mucosa, improved nasal mucosal thickness, and decreased mast cell infiltration. To explore the potential mechanism, ADELN treatment was associated with reduced IκB and p65 phosphorylation and decreased NF-κB nuclear translocation, suggesting that modulation of NF-κB signaling may contribute to the anti-inflammatory effects of ADELNs. <b>Conclusions:</b> This study successfully isolated and characterized ADELNs. Using a self-designed ultrasonic nebulization device for mouse nasal delivery, we showed that ADELNs inhibited cellular inflammation in vitro, alleviated symptoms and pathological injury in AR mice, and may exert anti-AR effects by suppressing the NF-κB signaling pathway. These findings provide a new strategy for AR treatment.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics and Extrapolation of NP-011 from Animal to Humans: A Novel Therapeutic Candidate Protein for Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Hyunjung Lee, Quyen Thi Tran, Bui Thi Tham, Min-Kyoung Kim, Hwi-Yeol Yun, Jung-Woo Chae, Jung-Hyuck Park, Soyoung Lee","doi":"10.3390/pharmaceutics18091194","DOIUrl":"10.3390/pharmaceutics18091194","url":null,"abstract":"<p><p><b>Background/Objective:</b> Metabolic dysfunction-associated steatohepatitis (MASH), an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), is characterized by progressive liver fibrosis and represents an important therapeutic target. NP-011 is a truncated recombinant human milk fat globule EGF factor 8 protein developed for the treatment of MASH-associated liver fibrosis. This study extrapolated the pharmacokinetics of NP-011 from animals to humans and retrospectively evaluated the predictions using Phase I clinical data. <b>Methods:</b> Population pharmacokinetic models were developed using plasma concentration-time data following the intravenous administration of NP-011 in mice, rats, and monkeys. Model performance was evaluated using goodness-of-fit diagnostics, visual predictive checks, and nonparametric bootstrap analyses. The human pharmacokinetic parameters were predicted using simple allometric scaling. The maximum lifespan potential-corrected scaling was evaluated as a supplementary sensitivity analysis. Predicted human concentration-time profiles and exposure parameters were retrospectively compared with observed data from the single ascending dose component of the Phase I data. The Phase I study was registered at ClinicalTrials.gov (NCT05387499). <b>Results:</b> A two-compartment model with first-order elimination described NP-011 pharmacokinetics in all three species. For a 70-kg adult, simple allometry predicted clearance, central volume of distribution, intercompartmental clearance, and peripheral volume of distribution values of 3.80 L/h, 2.88 L, 0.25 L/h and 24.61 L, respectively. Across the 0.25-4 mg dose range, the predicted median AUC_inf values were 1.62- to 1.96-fold higher than the corresponding observed medians, whereas the predicted median C_max values were 1.33- to 1.48-fold higher. Overall 17.1% of the observed concentrations were contained within the simulated 5th-95th percentile prediction intervals. The maximum lifespan potential correction resulted in greater overprediction of AUC_inf, with predicted-to-observed ratios of 2.38-2.89, whereas C_max predictions were unchanged. <b>Conclusions:</b> Simple allometry provided closer agreement with the observed Phase I exposure than maximum lifespan potential-corrected scaling. However, the systematic overprediction of exposure and limited coverage of the simulated prediction intervals indicate that these predictions should be interpreted cautiously. These findings support simple allometry as a practical approach for extrapolating the pharmacokinetics of NP-011 to healthy adults in early clinical development, although broader generalization requires further evaluation.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Thermoresponsive In Situ Salified Self-Nanoemulsifying Drug Delivery System of Olmesartan Medoxomil: Overcoming Leakage and Drug Trapping Limitations.","authors":"Abdelrahman Y Sherif, Mohammad A Altamimi, Ehab M Elzayat","doi":"10.3390/pharmaceutics18091195","DOIUrl":"10.3390/pharmaceutics18091195","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Solid self-nanoemulsifying drug delivery systems (SNEDDS) prepared by adsorption onto porous carriers are widely used to improve the oral delivery of poorly water-soluble drugs. However, this approach is limited by increased dosing volume and incomplete drug release. This study aims to develop a thermoresponsive in situ salified SNEDDS (T-IS-SNEDDS) that simultaneously prevents formulation leakage and overcomes the release limitations of conventional adsorption-based solidification. <b>Methods:</b> Excipients were selected by solubility screening of oils and surfactants. Sodium and calcium carbonate were evaluated for in situ salt formation. Adsorption-based solid SNEDDS and thermoresponsive formulations containing poloxamer 188 with propylene glycol or polyethylene glycol 400 were prepared. Droplet size was measured after aqueous dilution. Solid-state characterization used scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. In vitro dissolution performance was evaluated against the raw drug and adsorption-based formulations. <b>Results:</b> Imwitor 308 and Tween 80 exhibited the highest solubilization capacities. Sodium carbonate (10 mg/g) markedly increased the solubility of olmesartan medoxomil from 4.11 ± 0.11 to 46.01 ± 1.92 mg/g. Although liquid in situ salified SNEDDS achieved rapid dissolution (94.2 ± 1.8% at 10 min), adsorption-based solidification required four capsules and yielded incomplete drug release (67.76 ± 3.18%). Both thermoresponsive formulations accommodated the therapeutic dose in a single capsule and released ≈95% of the drug within 60 min. <b>Conclusions:</b> The combined in situ salified drug loading and thermoresponsive matrix strategy successfully enables single capsule administration while overcoming the incomplete release of adsorption-based solid SNEDDS.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism-Driven Design of Metal-Phenolic Networks: From Precision Assembly to Multidimensional Synergistic Therapy for Brain Diseases.","authors":"Mengyue Ni, Bo Hu, Di Zhu, Boya Li, Yijiang Jia, Yu Lu, Yuji Wang","doi":"10.3390/pharmaceutics18091192","DOIUrl":"10.3390/pharmaceutics18091192","url":null,"abstract":"<p><p><b>Background</b>: Brain disorders, such as glioblastoma, Alzheimer's disease and ischemic stroke, represent formidable challenges due to the highly restrictive blood-brain barrier (BBB) and the complex pathophysiological microenvironment, which severely compromise drug delivery and therapeutic outcomes. Metal-phenolic networks (MPNs), as a class of novel hybrid materials, hold great promise for overcoming brain delivery bottlenecks and enabling precise synergistic therapy by leveraging their unique physicochemical properties. However, a comprehensive synthesis of MPN designs tailored specifically to the distinct pathological mechanisms underlying brain disorders is currently lacking. <b>Methods</b>: In this review, we systematically outline the foundational building blocks of MPNs and their diverse nanostructure engineering strategies. Building on this, we closely align MPN customization with the four core pathological pillars of brain diseases, thoroughly summarizing advanced design strategies and synergistic therapeutic mechanisms. Additionally, we prospectively discuss emerging innovative approaches, including the targeting of neutrophil extracellular traps (NETs) to modulate the immunosuppressive tumor microenvironment. <b>Outlook</b>: Finally, we critically examine the pivotal obstacles hindering the clinical translation of MPNs, particularly concerning uncertainties in long-term biosafety and in vivo metabolism, metal-specific neurotoxicity and coordination-stability-governed metal release kinetics, challenges in quality control during scalable production, and the unpredictable interference of the protein corona. <b>Conclusions</b>: In this review, we provide a robust theoretical foundation for the rational design of mechanism-driven MPNs, while offering forward-looking perspectives to accelerate their clinical translation from bench to bedside for the precise management of brain diseases.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Optimization of Self-Nanoemulsifying Drug Delivery Systems to Enhance the Anti-Inflammatory Efficacy of <i>Derris scandens</i> (Roxb.) Benth. Extract.","authors":"Nattakanwadee Khumpirapang, Kantapich Srikham, Thapakorn Somboon, Krit Suknuntha, Daniela Gruľová, Neti Waranuch, Kornkanok Ingkaninan, Siriporn Okonogi","doi":"10.3390/pharmaceutics18091188","DOIUrl":"10.3390/pharmaceutics18091188","url":null,"abstract":"<p><p><b>Background/Objectives:</b><i>Derris scandens</i> (Roxb.) Benth. stem extract (DSE) is used in Thailand for musculoskeletal pain, but its bioactive, lupalbigenin, has limited aqueous solubility. This study aimed to develop a DSE-loaded self-nanoemulsifying drug delivery system (DSE-SNEDDS), characterized its nanoemulsions, and compared their anti-inflammatory activity and stability. <b>Methods:</b> Various extraction methods were compared to obtain a high yield of lupalbigenin. A D-optimal design was used to optimize SNEDDS composition based on the apparent solubility of lupalbigenin. The selected preconcentrate was diluted fivefold to prepare DSE nanoemulsion (DSE-NE). Droplet characteristics, RAW 264.7 cell viability, LPS-induced nitric oxide production, and 12-week stability at 4, 25, and 40 °C were assessed. <b>Results:</b> Ultrasound-assisted extraction gave the highest lupalbigenin content (108.69 ± 0.12 µg/mg DSE). The selected formulation contained 20% Lexol^® GT-865, 40% Kolliphor RH40, 30% Transcutol, and 10% ethanol. Fivefold dilution produced DSE-NE with a droplet size of 172.5 ± 0.3 nm and polydispersity index of 0.31 ± 0.01. Its IC₅₀ was 4735 µg/mL formulation (94.70 µg/mL DSE equivalent), compared with 31.57 µg/mL for DSE in DMSO. At 40 µg/mL DSE equivalent, DSE-NE and DSE in DMSO inhibited nitric oxide production by 78.79 ± 2.31% and 50.78 ± 2.95%, respectively; matched blank NE produced 36.53 ± 6.45% inhibition. During storage, the preconcentrate retained 95-96% of lupalbigenin and generated nanoemulsions with minimal size changes, whereas preformed DSE-NE retained 81-87% and showed greater droplet growth. <b>Conclusions:</b> These results support the selection of the preconcentrate as the preferred storage form for further topical formulation development. However, skin delivery, dermal safety, and topical efficacy remain to be established.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narrow Therapeutic Index Drugs: Regulatory Frameworks, Bioequivalence, and Model-Informed Precision Dosing.","authors":"Mengmeng Liu, Zhe Wang, Yongbo Chen, Yuqi Jia, Lei Xu, Haojie Xu, Jueyu Li, Libo Zhao","doi":"10.3390/pharmaceutics18091190","DOIUrl":"10.3390/pharmaceutics18091190","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Narrow therapeutic index (NTI) drugs are characterized by a small margin between effective and toxic exposure. This review aimed to summarize international definitions and regulatory frameworks for NTI drugs, compare bioequivalence requirements for generic NTI products, and evaluate the role of model-informed approaches in precision dosing and lifecycle risk management. <b>Methods</b>: A structured literature search was conducted in PubMed, MEDLINE, Embase, Web of Science, Scopus, and the China National Knowledge Infrastructure from database inception to 30 June 2026. Official documents from major regulatory authorities were also reviewed. Evidence relating to NTI drug classification, bioequivalence, interchangeability, therapeutic drug monitoring, population pharmacokinetics, physiologically based pharmacokinetics, machine learning, and hybrid modeling was included. <b>Results</b>: Definitions, drug lists, study designs, and bioequivalence criteria varied substantially across jurisdictions. Several authorities use narrowed acceptance ranges, whereas China and the United States apply fully replicated crossover designs with reference-scaled average bioequivalence, average bioequivalence constraints, and within-subject variability comparisons for selected NTI drugs. Population pharmacokinetic and Bayesian approaches remain the most mature tools for therapeutic drug monitoring and individualized dosing. Physiologically based models support drug-drug interaction prediction, special-population extrapolation, virtual bioequivalence, and clinically relevant formulation specifications. Machine-learning and hybrid models improve exposure, dose, and toxicity-risk prediction, but most evidence remains retrospective and externally limited. <b>Conclusions</b>: NTI drug regulation and clinical management remain heterogeneous. Greater international harmonization, standardized model validation, prospective clinical evaluation, and integration of regulatory, formulation, and patient-level data are needed to support safer substitution and more reliable precision dosing.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives.","authors":"Qi Guo, Lushu Chen, Ziyan Wu, Qiuyang Zhang, Jinsong Xue, Huiying Zhang","doi":"10.3390/pharmaceutics18091189","DOIUrl":"10.3390/pharmaceutics18091189","url":null,"abstract":"<p><p>Ocular diseases remain a major global health challenge with substantial unmet therapeutic needs. Small nucleic acid therapeutics offer a precise strategy to regulate disease-related mRNAs or noncoding RNAs through base pairing, thereby modulating protein expression at the RNA level. Major modalities include antisense oligonucleotides, small interfering RNAs, microRNA-based therapeutics, small activating RNAs, and nucleic acid aptamers, which act through RNA degradation, RNA interference, splicing modulation, microRNA regulation, transcriptional activation, or structure-dependent target binding. These properties make them attractive for ocular diseases involving genetic defects, pathological angiogenesis, inflammation, fibrosis, or neurodegeneration. However, their clinical translation in ophthalmology remains limited by poor molecular stability, insufficient tissue retention, immune activation, off-target effects, and inefficient delivery to target ocular tissues. Rational oligonucleotide design, appropriate local administration routes, and optimized delivery platforms are therefore essential for improving stability, tissue penetration, cellular uptake, and therapeutic durability. This review summarizes the major classes, mechanisms, chemical modification strategies, ocular delivery systems, and therapeutic applications of small nucleic acid drugs in ophthalmology. We also discuss lessons from clinical successes and failures and propose future directions for safe, durable, and individualized ocular therapy.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13610481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Pharmaceutical Perspectives on Quinones as Antioxidant and Antidiabetic Agents in Diabetes and Its Complications.","authors":"Krishnendu Adhikary, Thirtsha Shohani Godwin, Adsaya Karunanithi, Riya Sarkar, Md Abubakar, Sayoni Nag, Saurav Barman, Nilanjana Datta, Rajkumar Maiti","doi":"10.3390/pharmaceutics18091191","DOIUrl":"10.3390/pharmaceutics18091191","url":null,"abstract":"<p><p><b>Background</b>: Diabetes mellitus (DM) is an extremely complex metabolic disorder, with many factors contributing to persistent hyperglycaemia, redox dysregulation, and micro- and macrovascular damage over time. There is growing evidence that oxidative stress is one of the main mechanisms of β-cell damage, insulin resistance, and consequent tissue damage, pointing to the need for therapies to modulate metabolic and redox responses. The extensive nature of quinones has revealed that they can be potential dual-acting redox-active compounds that may have antioxidant and antidiabetic activities. <b>Objectives</b>: This review aims to evaluate quinones from a pharmaceutical perspective, considering the chemical diversity and structure-activity relationships, the physicochemical parameters pertinent to drug development, and the mechanisms of action in terms of glucose homeostasis, insulin signalling, mitochondrial protection, and glycoxidative damage. <b>Methods</b>: Narrative review of the evidence from medicinal chemistry, experimental pharmacology, pharmacokinetics, formulation research, and clinical studies of the potential role of quinones in diabetes and its complications. The paper addresses the relationship between chemical structure and biological activity, redox-dependent mechanisms of action, tissue-protective actions, challenges associated with delivery, toxicity, and recent approaches to formulation. <b>Results</b>: Quinones influence several processes implicated in diabetes, including mitochondrial dysfunction, oxidative stress, pancreatic β-cell injury, insulin signalling impairment, AGE-RAGE activation, and chronic inflammation. Currently, CoQ10 has the strongest evidence in humans, while thymoquinone (TQ), pyrroloquinoline quinone (PQQ), anthraquinones, and mitochondria-targeted derivatives have mainly cellular and animal studies to support them. Low solubility, variable systemic exposure, rapid metabolism, and the potential for pro-oxidant effects at high concentrations continue to hamper therapeutic development of these compounds. <b>Conclusions</b>: Future research scopes will rely on rational derivatisation, precision delivery technologies, and clinically validated safety frameworks to translate redox pharmacology into effective therapeutic interventions.</p>","PeriodicalId":19894,"journal":{"name":"Pharmaceutics","volume":"18 9","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}