Pharmaceuticals最新文献

{"title":"Development and Evaluation of Hydrogel-Based Sulfasalazine-Loaded Nanosponges for Enhanced Topical Psoriasis Therapy.","authors":"Sunil Kumar, Anroop B Nair, Varsha Kadian, Pooja Dalal, Babu Lal Jangir, Bandar Aldhubiab, Rashed M Almuqbil, Ahmed S Alnaim, Nouf Alwadei, Rekha Rao","doi":"10.3390/ph18030391","DOIUrl":"10.3390/ph18030391","url":null,"abstract":"<p><p><b>Background:</b> The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. <b>Methods:</b> SLZ-loaded nanosponges were prepared by the melt polymerization method and evaluated for physiochemical characteristics, drug release, and cytocompatibility. The selected nanosponges (SLZ-NS4) were transformed to hydrogel and further evaluated for rheology, texture, safety, skin permeability, and in vivo for anti-psoriatic effect in mouse tail and imiquimod-induced psoriasis-like inflammation models in mice. <b>Results:</b> Physiochemical data confirms nanoscale architecture, drug inclusion in nanosponges, crystalline structure, and formulation stability. The release profile of SLZ-NS4 revealed sustained release behavior (22.98 ± 2.24% in 3 h). Cytotoxicity assays indicated negligible toxicity against THP1 cells, resulting in higher viability of cells than pure SLZ (<i>p</i> < 0.05). The HET-CAM assay confirmed the safety, while confocal laser scanning microscopy demonstrated deeper skin permeation of SLZ. In the mouse tail model, a remarkable decline in relative epidermal thickness, potential improvement in percent orthokeratosis, and drug activity with respect to control was observed in animals treated with SLZ-NS4 hydrogel. The efficiency of the developed SLZ-NS4-loaded hydrogel in treating psoriasis was confirmed by the decline in PASI score (81.68 ± 3.61 and 84.86 ± 5.74 with 1 and 2% <i>w</i>/<i>v</i> of SLZ-NS-HG). Histopathological analysis and assessment of oxidative stress markers revealed the profound anti-psoriatic potential of the fabricated SLZ-NS4 hydrogel. <b>Conclusions:</b> These findings highlight the profound potential of the developed delivery system as an effective topical therapy for psoriasis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721078","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":"The Cholinergic Amelioration of Sepsis-Induced Baroreflex Dysfunction and Brainstem Inflammation Is Negated by Central Adenosine A3 Receptors.","authors":"Amany E El-Naggar, Mai M Helmy, Sahar M El-Gowilly, Mahmoud M El-Mas","doi":"10.3390/ph18030388","DOIUrl":"10.3390/ph18030388","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Sepsis has been shown to depress arterial baroreceptor function, and this effect is counterbalanced by the cholinergic anti-inflammatory pathway. Considering the importance of central adenosine receptors in baroreceptor function, this study tested whether central adenosine A3 receptors (A3ARs) modulate the cholinergic-baroreflex interaction in sepsis and whether this interaction is modulated by mitogen-activated protein kinases (MAPKs) and related proinflammatory cytokines. <b>Methods</b>: Sepsis was induced by cecal ligation and puncture (CLP) and rats were instrumented with femoral and intracisternal (i.c.) catheters. Baroreflex sensitivity (BRS) was measured 24 h later in conscious animals using the vasoactive method, which correlates changes in blood pressure caused by i.v. phenylephrine (PE) and sodium nitroprusside (SNP) to concomitant reciprocal changes in heart rate. <b>Results</b>: The reduction in reflex bradycardic (BRS-PE), but not tachycardic (BRS-SNP), responses elicited by CLP was reversed by i.v. nicotine in a dose-related manner. The BRS-PE effect of nicotine was blunted following intracisternal administration of IB-MECA (A3AR agonist, 4 µg/rat). The depressant action of IB-MECA on the BRS facilitatory action of nicotine was abrogated following central inhibition of MAPK-JNK (SP 600125), PI3K (wortmannin), and TNFα (infliximab), but not MAPK-ERK (PD 98059). Additionally, the nicotine suppression of sepsis-induced upregulation of NFκB and NOX2 expression in the nucleus tractus solitarius (NTS) was negated by A3AR activation. The molecular effect of IB-MECA on NFκB expression disappeared in the presence of SP 600125, wortmannin, or infliximab. <b>Conclusions</b>: The central PI3K/MAPK-JNK/TNFα pathway contributes to the restraining action of A3ARs on cholinergic amelioration of sepsis-induced central neuroinflammatory responses and impairment of the baroreceptor-mediated negative chronotropism.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721253","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":"The Effect of Ethanolic Extract of Brazilian Green Propolis and Artepillin C on Cytokine Secretion by Stage IV Glioma Cells Under Hypoxic and Normoxic Conditions.","authors":"Małgorzata Kłósek, Anna Kurek-Górecka, Radosław Balwierz, Grażyna Pietsz, Zenon P Czuba","doi":"10.3390/ph18030389","DOIUrl":"10.3390/ph18030389","url":null,"abstract":"<p><p><b>Background:</b> The majority of gliomas are astrocytic in nature. Gliomas have the lowest survival rate among all tumors of the central nervous system (CNS), characterized by high aggressiveness and poor response to treatment. The tumor microenvironment is a source of cytokines such as IL-6, IFN-γ, VEGF, and PDGF-BB, secreted mainly by tumor and immune cells. These cytokines play a significant role in angiogenesis, invasion, and metastasis formation. In vitro and in vivo studies have shown that Brazilian green propolis, derived from <i>Baccharis dracunculifolia</i> DC and rich in artepillin C, exhibits anti-inflammatory, antimicrobial, chemopreventive, and anticancer activities. Additionally, it can penetrate the blood-brain barrier, demonstrating neuroprotective effects. The aim of the present study was to determine the concentration of selected cytokines produced by astrocytes of the CCF-STTG1 cell line, isolated from the brain of a patient with stage IV glioma (astrocytoma). <b>Methods:</b> The cytotoxicity of the EEP-B was evaluated using the MTT assay. Astrocytes were stimulated with LPS at a final concentration of 200 ng/mL and/or IFN-α at 100 U/mL, followed by incubation with EEP-B (25-50 µg/mL) and artepillin C (25-50 µg/mL) under 2-h hypoxia and normoxia conditions. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine kit. <b>Results:</b> The absence of cytotoxic effects of EEP-B and artepillin C on human astrocytes of the CCF-STTG1 lineage was demonstrated. Stimulation with LPS, IFN-α, and their combination (LPS + IFN-α) significantly increased the secretion of the tested cytokines compared to the control cell line. The most pronounced and statistically significant reduction in cytokine levels, particularly IL-6 and VEGF, was observed following EEP-B treatment at both tested concentrations under both hypoxic and normoxic conditions. <b>Conclusions:</b> Brazilian green propolis may serve as a potential immunomodulator in combination therapies for gliomas of varying malignancy grades.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721254","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":"Gallium-Labeled PET Radiopharmaceuticals in Cardiovascular Disease.","authors":"Matthieu Bailly, Anne Claire Dupont, Guillaume Domain, Diane Darsin-Bettinger, Maxime Courtehoux, Gilles Metrard, Alain Manrique, Jonathan Vigne","doi":"10.3390/ph18030387","DOIUrl":"10.3390/ph18030387","url":null,"abstract":"<p><p>Gallium-labeled positron emission tomography (PET) probes targeting activated fibroblasts or somatostatin receptor expression are frequently used for varying applications in oncology. With the widespread availability of ⁶⁸Ge/⁶⁸Ga generators and cold kits, ⁶⁸Ga tracers have become a main tool in molecular imaging. These tracers, such as [⁶⁸Ga]Ga-DOTA-TATE, [⁶⁸Ga]Ga-FAPI, and [⁶⁸Ga]Ga-pentixafor, allow targeted imaging of the key pathological processes, including inflammation, fibrosis, and necrosis. This review highlights their potential in conditions like myocardial infarction, cardiac sarcoidosis, myocarditis, and other cardiomyopathies. Clinical and preclinical studies underscore their utility in visualizing active disease processes, predicting outcomes, and guiding therapeutic strategies. However, challenges remain, including the need for standardization, larger clinical trials, and integration into routine practice. These advancements position ⁶⁸Ga-based PET as a promising modality for enhancing diagnostic precision and personalized treatment in cardiovascular disease.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721109","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":"Huperzine A Production and Acetylcholinesterase Inhibition by <i>Phlegmariurus taxifolius</i> Cell Suspension Culture: A Comparative Study in Flasks and an Airlift Bioreactor.","authors":"Rocío Del Carmen Pérez Aguilar, Talia Rodríguez Salgado, Olga Lidia Cruz-Miranda, Alexis Uriel Soto Díaz, Ariadna Zenil Rodríguez, Lamine Bensaddek, Christian Carreño-Campos, María Luisa Villarreal, Anabel Ortiz-Caltempa, Alexandre Toshirrico Cardoso-Taketa","doi":"10.3390/ph18030383","DOIUrl":"10.3390/ph18030383","url":null,"abstract":"<p><p><b>Background</b>: The callus cultures from the fronds of the lycophyte <i>Phlegmariurus taxifolius</i> produce the huperzine A (HupA) alkaloid, which is used in Alzheimer's disease treatment. This study aimed to establish the growth kinetics and HupA production by the newly HupS21 cell line grown in 250 mL flasks and in a 2 L airlift bioreactor. <b>Methods</b>: Batch-type kinetics were carried out for 60 days in 250 mL flasks and for 20 days in a 2 L airlift bioreactor. Measurements of dry weight (DW), specific growth rate (μ), doubling time (dt), pH, carbohydrate consumption, and HupA quantification were performed. The acetylcholinesterase (AChE) inhibitory assay of the HupS21 alkaloidal extract was determined. <b>Results</b>: The 250 mL flasks kinetic reached a maximum cell growth of 8.17 g/L DW, with a μ of 0.045 day^-1 and a dt of 15.40 days. The maximum HupA production was of 2.03 μg/g DW at day 45. In the 2 L airlift reactor, a maximum growth of 16.70 g/L DW, a μ of 0.062 day^-1, a dt of 11.20 days, and HupA production of 2.48 μg/g DW at day 15 were obtained. The alkaloidal extract from the HupS21 cell line at 100 μg/mL showed an AChE inhibitory activity of 85.6 ± 1.27%. <b>Conclusions</b>: The airlift reactor outperformed the flask cultures in maximum cell growth, specific growth rate, doubling time, and HupA production. To our knowledge, this research is the first report on the establishment of suspension cell cultures of <i>P. taxifolius</i> in shaken flasks and in an airlift bioreactor, providing a foundation for scaling up HupA production for pharmaceutical use.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721103","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":"Glioblastoma Tumor Microenvironment and Purinergic Signaling: Implications for Novel Therapies.","authors":"Martina Bedeschi, Elena Cavassi, Antonino Romeo, Anna Tesei","doi":"10.3390/ph18030385","DOIUrl":"10.3390/ph18030385","url":null,"abstract":"<p><p>Glial-origin brain tumors, particularly glioblastomas (GBMs), are known for their devastating prognosis and are characterized by rapid progression and fatal outcomes. Despite advances in surgical resection, complete removal of the tumor remains unattainable, with residual cells driving recurrence that is resistant to conventional therapies. The GBM tumor microenviroment (TME) significantly impacts tumor progression and treatment response. In this review, we explore the emerging role of purinergic signaling, especially the P2X7 receptor (P2X7R). Due to its unique characteristics, it plays a key role in tumor progression and offers a potential therapeutic strategy for GBM through TME modulation. We discuss also the emerging role of the P2X4 receptor (P2X4R) as a promising therapeutic target. Overall, targeting purinergic signaling offers a potential approach to overcoming current GBM treatment limitations.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721119","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":"Dezocine and Addiction: Friend or Foe?","authors":"Wayne Childers, Khaled Elokely, Magid Abou-Gharbia","doi":"10.3390/ph18030386","DOIUrl":"10.3390/ph18030386","url":null,"abstract":"<p><p>The neurological effects of opium were first described over 8000 years ago. Morphine was isolated in 1803 and by the mid-1800s had become both a pain-relieving blessing and an addictive curse. As part of the crusade to identify safer and more reliable alternatives to morphine, dezocine (Dalgan^®) was marketed in the US in 1986. Its use was discontinued in the US in 2011 without revealing the reasons, but it remains one of the most widely used analgesic agents in China today. Dezocine's unique pharmacology makes it an effective analgesic with limited opioid-associated side effects and little or no reported potential for dependence and addiction. In addition, dezocine's blocking effect on serotonin and norepinephrine transporters recommends its further exploration as a potential treatment for various chronic and neuropathic pain conditions. Most recently, data suggest that dezocine might represent a viable treatment for addiction management. This report focuses on the data supporting dezocine's non-addictive profile and its potential use to treat opioid addiction and withdrawal, as well as recent efforts to generate formulations of dezocine that support sub-chronic and chronic dosing.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11946148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721081","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":"AMPA Receptor Modulation in the Treatment of High-Grade Glioma: Translating Good Science into Better Outcomes.","authors":"Daniel P Radin","doi":"10.3390/ph18030384","DOIUrl":"10.3390/ph18030384","url":null,"abstract":"<p><p>Glioblastoma (GB) treatment, despite consisting of surgical resection paired with radiation, temozolomide chemotherapy and tumor-treating fields, yields a median survival of 15-20 months. One of the more recently appreciated hallmarks of GB aggressiveness is the co-opting of neurotransmitter signaling mechanisms that normally sustain excitatory synaptic communication in the CNS. AMPA-glutamate receptor (AMPAR) signaling governs the majority of excitatory synaptic activity in the mammalian brain. AMPAR activation in glioma cells activates cellular pathways that enhance proliferation and invasion and confer resistance to approved GB therapeutics. In addition, this review places a specific emphasis on discussing the redefined GB cytoarchitecture that consists of neuron-to-glioma cell synapses, whose oncogenic activity is driven by AMPAR activation on glioma cells, and the discovery of tumor microtubes, which propagate calcium signals throughout the tumor network in order to enhance resistance to complete surgical resection and radiotherapy. These new discoveries notwithstanding, some evidence suggests that AMPAR activation can produce excitotoxicity in tumor cells. This disparity warrants a closer examination at how AMPAR modulation can be leveraged to produce more durable outcomes in the treatment of GB and tumors in peripheral organs that express AMPAR.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721067","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":"Extraction Yields of Psilocybin and Psilocin: A Short Review of Current Methods and Their Implications.","authors":"Taynah P Galdino, Lucas C Oliveira, Mateus A Luz, Raquel A Jesus, Eunice P N Lima, Maria C M Torres, Katia Sivieri, Victor I Afonso, João M P Q Delgado, Antonio G B Lima, Suédina M L Silva, Marcus V L Fook","doi":"10.3390/ph18030380","DOIUrl":"10.3390/ph18030380","url":null,"abstract":"<p><p>The growing body of evidence supporting the therapeutic efficacy of psychoactive substances, like psilocybin, has driven significant interest in recent decades due to their low toxicity and potential applications in treating various mental health disorders. However, producing pharmaceutical-grade psilocybin remains challenging, with three primary approaches: chemical synthesis, biosynthesis, and extraction from <i>Psilocybe</i> mushroom fruiting bodies. This systematic review evaluates the extraction and quantification methods for psilocybin and psilocin, aiming to contribute to the development of standardized protocols that ensure compound quality and purity. A total of 25 relevant studies were selected from an initial pool of 9152 publications indexed in platforms such as Scopus, ScienceDirect, Web of Science, and PubMed. The findings indicate that both the extraction method and the choice of mushroom species significantly influence compound yields. Ultrasonic bath extraction was identified as the most efficient technique, particularly for species including <i>Psilocybe cyanescens</i> and <i>Psilocybe cubensis</i>. High-performance liquid chromatography (HPLC) was the most-used method for identifying and quantifying these compounds. Furthermore, polar solvents were critical for effective solubilization, with parameters such as temperature, solvent-to-material ratio, and extraction time playing key roles in optimizing yields. This review serves as a key scientific reference for advancing research, enhancing analytical precision, and ensuring reproducibility through the standardization of extraction and quantification protocols.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11945839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721085","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":"Polylactic-Co-Glycolic Acid/Alginate/Neem Oil-Reduced Graphene Oxide as a pH-Sensitive Nanocarrier for Hesperidin Drug Delivery: Antimicrobial and Acute Otitis Media Assessments.","authors":"Saeed Abdul Kareem Saeed Al-Zuhairy, Sammar Fathy Elhabal, Mohamed Fathi Mohamed Elrefai, Sandra Hababeh, Jakline Nelson, Marwa Fady, Nahla A Elzohairy, Tassneim M Ewedah, Ibrahim S Mousa, Ahmed Mohsen Elsaid Hamdan","doi":"10.3390/ph18030381","DOIUrl":"10.3390/ph18030381","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled drug delivery in response to external stimuli, such as pH variations. <b>Methods</b>: Graphene oxide (GO)-based nanocarriers that encapsulate hesperidin (HSP) were further coated with a polylactic-co-glycolic acid/alginate (PLGA-Alg) hydrogel before being integrated into a green neem oil (N.O.) double emulsion to produce a synergistic effect and then characterized by different assays. <b>Results</b>: The nanocarriers exhibited a substantial particle size (168 ± 0.32 nm), with high encapsulation (89.86 ± 0.23%) and a zeta potential of 37 ± 0.43 mV. In vitro release studies conducted over 96 h indicated a sustained HSP release of 82% at pH 5.4 and 65% at pH 7.4. The GO-HSP-loaded neem oil double emulsion formulation exhibits substantial antibacterial activity, as evidenced by inhibition zones of 39 ± 0.02 mm against <i>Staphylococcus epidermidis</i>, and considerable antifungal activity against <i>Candida albicans</i>, with an inhibition zone of 43 ± 0.13 mm, along with biofilm inhibition activity. The formulation demonstrated antioxidant activity (5.21 µg/mL) and increased cell viability (90-95%) while maintaining low cytotoxicity in HSE-2 cells. A histopathological analysis confirmed that treatment with the nanocarriers reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, TLR4, IL-6) and raised the levels of antioxidant markers (Nrf-2, SOD) in an in vivo rat model of otitis media. <b>Conclusions</b>: GO-based nanocarriers integrated into a neem oil double emulsion and coated with PLGA-Alg hydrogel deliver hesperidin with sustained release and enhanced antibacterial, antifungal, and antioxidant properties. This formulation may be used to treat otitis media and other oxidative stress diseases.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721246","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}