AAPS PharmSciTech最新文献

{"title":"Nano-Engineered Epigallocatechin Gallate (EGCG) Delivery Systems: Overcoming Bioavailability Barriers to Unlock Clinical Potential in Cancer Therapy","authors":"Mohammad Qutub,&nbsp;Ujban Md Hussain,&nbsp;Amol Tatode,&nbsp;Tanvi Premchandani,&nbsp;Rahmuddin Khan,&nbsp;Milind Umekar,&nbsp;Jayshree Taksande,&nbsp;Priyanka Singanwad","doi":"10.1208/s12249-025-03145-0","DOIUrl":"10.1208/s12249-025-03145-0","url":null,"abstract":"<div><p><i>Epigallocatechin gallate</i> (EGCG), a bioactive polyphenol derived from <i>Camellia sinensis</i>, exhibits multimodal anticancer activity through mechanisms such as apoptosis induction, metastasis suppression, and chemoresistance reversal. Despite its therapeutic promise, clinical application is constrained by rapid metabolism, poor bioavailability, and inconsistent biodistribution. Recent advances in nanotechnology have enabled the development of innovative delivery systems including pH-responsive nanoparticles, lipid-polymer hybrids, and ligand-functionalized carriers that enhance EGCG stability, tumor targeting, and bioavailability by 3- to fivefold in preclinical models. These platforms also facilitate synergistic co-delivery with chemotherapeutics like doxorubicin, amplifying cytotoxicity and overcoming multidrug resistance. Mechanistically, EGCG modulates oncogenic pathways via NF-κB suppression, caspase activation, and MMP-9 downregulation, demonstrating efficacy across diverse cancer types. However, translational challenges persist, such as nanoparticle toxicity, variable tumor accumulation, and insufficient penetration in hypoxic microenvironments. Regulatory hurdles, including the lack of harmonized global standards for herbal medicinal products, further complicate clinical adoption. To bridge these gaps, future research must prioritize scalable cGMP-compliant manufacturing, rigorous preclinical toxicity profiling, and robust clinical trials to validate safety and efficacy. Addressing these issues could position nanoengineered EGCG as a paradigm-shifting therapy in precision oncology, aligning with ESCOP’s mission to integrate evidence-based phytomedicines into conventional cancer care. This review underscores the necessity of interdisciplinary collaboration to standardize phytopreparations, refine regulatory frameworks, and advance biomarker-driven clinical validation, ultimately unlocking the full potential of EGCG in modern therapeutics.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073858","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":"Fabrication of 3D Printed Microneedle Patch for the Simultaneous Delivery and Detection of Melatonin from Interstitial Fluid","authors":"Shreya Chauhan,&nbsp;Venkata Vamsi Krishna Venuganti","doi":"10.1208/s12249-025-03139-y","DOIUrl":"10.1208/s12249-025-03139-y","url":null,"abstract":"<div><p>Interstitial fluid (ISF) offers a potential alternative to invasive blood sample collection for biomolecule analysis. Microneedle (MN) patch application can collect ISF in a minimally invasive manner. Polyethylene glycol diacrylate MN patch was fabricated using optimized masked stereolithography-based 3D printing technique. Different 3D printing parameters including ink formula, exposure time, layer thickness, lift speed and distance, printing angle were optimized to fabricate pyramidal MN array. MN patch was characterized for design features, mechanical strength, <i>in vitro, ex vivo</i> and <i>in vivo</i> aspiration of fluid. MN patch aspirated 15 ± 2 µl ISF after application for 10 min in the rat model. Circadian rhythm controlling melatonin hormone was analyzed from ISF. The melatonin concentration ranged from 81 ± 13 to 178 ± 11 pg/ml and 94 ± 20 to 202 ± 6 pg/ml in ISF and serum from light to dark cycle, respectively. Furthermore, two different concentrations of melatonin were loaded in the MN patch during the 3D printing process. The two patches, blank MN patch for collection of ISF for melatonin detection (melatonin aspiration patch) and melatonin loaded patch for delivery (melatonin delivery patch) were simultaneously applied on the rat. Melatonin concentration increased by 4.6 and sixfold in ISF and serum, respectively after application of 20 µg melatonin MN patch, which was determined by blank MN patch application. Taken together, mSLA 3D printing technique can be used to fabricate melatonin loaded MN patch to deliver and collect ISF for melatonin analysis.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144073871","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":"The Role of Artificial Intelligence in Drug Discovery and Pharmaceutical Development: A Paradigm Shift in the History of Pharmaceutical Industries","authors":"Nithin Vidiyala,&nbsp;Pavani Sunkishala,&nbsp;Prashanth Parupathi,&nbsp;Dinesh Nyavanandi","doi":"10.1208/s12249-025-03134-3","DOIUrl":"10.1208/s12249-025-03134-3","url":null,"abstract":"<div><p>In today’s world, with an increasing patient population, the need for medications is increasing rapidly. However, the current practice of drug development is time-consuming and requires a lot of investment by the pharmaceutical industries. Currently, it takes around 8–10 years and $3 billion of investment to develop a medication. Pharmaceutical industries and regulatory authorities are continuing to adopt new technologies to improve the efficiency of the drug development process. However, over the decades the pharmaceutical industries were not able to accelerate the drug development process. The pandemic (COVID-19) has taught the pharmaceutical industries and regulatory agencies an expensive lesson showing the need for emergency preparedness by accelerating the drug development process. Over the last few years, the pharmaceutical industries have been collaborating with artificial intelligence (AI) companies to develop algorithms and models that can be implemented at various stages of the drug development process to improve efficiency and reduce the developmental timelines significantly. In recent years, AI-screened drug candidates have entered clinical testing in human subjects which shows the interest of pharmaceutical companies and regulatory agencies. End-end integration of AI within the drug development process will benefit the industries for predicting the pharmacokinetic and pharmacodynamic profiles, toxicity, acceleration of clinical trials, study design, virtual monitoring of subjects, optimization of manufacturing process, analyzing and real-time monitoring of product quality, and regulatory preparedness. This review article discusses in detail the role of AI in various avenues of the pharmaceutical drug development process, its limitations, regulatory and future perspectives.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Optimization of Stimuli-Responsive Fenugreek/Carrageenan-Co-poly (Methacrylate) Hydrogel Matrices for Controlled Delivery of 5-Fluorouracil","authors":"Muhammad Arslan,&nbsp;Muhammad Umer Ashraf,&nbsp;Ayman M. Al-Qaaneh,&nbsp;Aysha Aslam,&nbsp;Asif Mahmood,&nbsp;Hira Ijaz,&nbsp;Rai Muhammad Sarfraz,&nbsp;Mohamed M. Salem,&nbsp;Milad A. Mezher,&nbsp;Mounir M. Bekhit","doi":"10.1208/s12249-025-03128-1","DOIUrl":"10.1208/s12249-025-03128-1","url":null,"abstract":"<div><p>This study developed novel, stimuli-responsive, biocompatible fenugreek/carrageenanco-poly(methacrylate) hydrogels via free radical polymerization for pH-regulated 5-FU delivery. The hydrogels were evaluated for drug loading (75.2–96.39%), swelling kinetics, sol–gel fraction, electrolyte responsiveness, porosity, and <i>in vitro</i> drug release. Analytical techniques (FTIR, SEM, PXRD, DSC/TGA) confirmed hydrogel formation, drug-excipient compatibility, and thermal stability. FTIR verified cross-linking and 5-FU incorporation, while DSC/TGA and PXRD indicated reduced drug crystallinity and transition to an amorphous form. SEM revealed rough surfaces with porous networks, supporting high drug loading. The hydrogels exhibited pH-responsive swelling, with higher swelling at pH 7.4 (following second-order kinetics) and minimal swelling at pH 1.2. They also responded to monovalent and divalent cations. <i>In vitro</i> release at pH 7.4 showed controlled 5-FU delivery (68.40–96.81%) over 36 h, following non-Fickian diffusion and Higuchi kinetics. Acute oral toxicity studies confirmed biocompatibility and safety. These findings demonstrate that fenugreek/carrageenan-co-poly(methacrylate) hydrogels are promising biocompatible carriers for targeted, controlled 5-FU delivery, offering a safer option for colorectal cancer treatment and other chemotherapy regimens.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944257","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":"Dasatinib Pharmacokinetics and Advanced Nanocarrier Strategies: from Systemic Limitations to Targeted Success","authors":"Mahesha Keerikkadu,&nbsp;Pragathi Devanand Bangera,&nbsp;Vamshi Krishna Tippavajhala,&nbsp;Mahalaxmi Rathnanand","doi":"10.1208/s12249-025-03130-7","DOIUrl":"10.1208/s12249-025-03130-7","url":null,"abstract":"<div><p>Dasatinib (DSB) is a second-generation tyrosine kinase inhibitor widely used for treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Though clinically effective, DSB has some pharmacokinetic drawbacks evidenced by rapid systemic clearance, low oral bioavailability, and poor aqueous solubility requiring high doses for therapeutic action. Novel formulation strategies like solid dispersions, liposomal formulations, and PEGylated and hybrid nanoparticles enhance DSB's pharmacokinetic and pharmacodynamic profiles by enhancing drug solubility, stability, and controlled release. In addition, through these targeted drug-delivery systems based on ligand-functionalized nanoparticles and antibody–drug conjugates-the tumor-targeted DSB is allowed selective accumulation at the tumor site, causing fewer off-target effects and lessening systemic toxicity while maximizing effectiveness. These approaches are geared toward utilizing nanotechnology to improve intracellular drug uptake and extend the circulation time to optimize antitumor efficacy. Overall, those advances in drug delivery systems could greatly boost the therapeutic efficacy of DSB by providing better bioavailability, controlled release, and targeted distribution. Such advances would increase treatment success in CML and Ph + ALL and expand DSB's potential clinical applications toward other malignancies. Research concerning the delivery of DSB with nanocarriers and ligand-mediated targeting strategies should bear further fruits to augment DSB therapy in oncology.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-025-03130-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Electrosprayed Janus Particles for Combined Photo-Chemotherapy","authors":"Brenda Sanchez-Vazquez,&nbsp;Adérito J. R. Amaral,&nbsp;Deng-Guang Yu,&nbsp;George Pasparakis,&nbsp;Gareth R. Williams","doi":"10.1208/s12249-025-03137-0","DOIUrl":"10.1208/s12249-025-03137-0","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944293","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":"AG86 Peptide-modified Reactive Oxygen Species-responsive Polymer Nanovesicles for Transdermal Delivery of Hydrophilic Ergothioneine to Basal Keratinocytes","authors":"Junlong Chen,&nbsp;Yiqing Long,&nbsp;Xiaozeliang Zhou,&nbsp;Zongning Yin","doi":"10.1208/s12249-025-03122-7","DOIUrl":"10.1208/s12249-025-03122-7","url":null,"abstract":"<div><p>This study aims to develop a multifunctional polymer nanovesicle system, AG86-β-glucan-poly(methionine-b-carboxybetaine) (AGPMC), which integrates AG86 peptide (a targeting ligand for the α6β4 integrin on basal keratinocytes) and reactive oxygen species (ROS) responsiveness to enhance the transdermal delivery of ergothioneine (EGT). The objective is to overcome the limitations of hydrophilic drug delivery and provide a targeted, ROS-triggered strategy for treating skin lipofuscin. AGPMC was synthesized via RAFT and ROP polymerization and self-assembles into stable nanovesicles (ANVs). Physicochemical characterization confirmed that the unloaded ANVs have an average size of 106.17 ± 3.26 nm and a polydispersity index (PDI) of 0.261 ± 0.027, with excellent stability and clear ROS-triggered structural responsiveness. After EGT loading, the nanovesicles exhibited a size of 140.10 ± 3.33 nm and a PDI of 0.217 ± 0.008. <i>In vitro</i> studies using HaCaT cells demonstrated a significant enhancement in cellular uptake, with an increase of up to 2.2-fold compared to free FSS (<i>p</i> &lt; 0.0001), as well as effective ROS scavenging and minimal cytotoxicity. The endocytosis mechanism study revealed that ANVs are primarily taken up via energy-dependent active transport, with caveolae-mediated endocytosis being the main pathway. Moreover, transdermal delivery studies confirmed that EGT-loaded nanovesicles significantly improved drug penetration through the stratum corneum. This work represents the first application of the AG86-conjugated nanovesicles for keratinocyte-targeted delivery, combined with ROS responsiveness. The “Loading-Targeting-Responding “ strategy holds significant potential for enhancing hydrophilic drug delivery and offers a promising approach for treating age-related skin lipofuscin accumulation.</p><h3>Graphical Abstract</h3><p>Targeted delivery of EGT via the “Loading-Targeting-Responding” strategy.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925676","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":"Oleogel-mediated Topical Administration of Roflumilast and Paclitaxel as a Synergistic Strategy to Combat Imiquimod-induced Psoriasis","authors":"Wenxiu Pan,&nbsp;Yunyi Shi,&nbsp;Fei Sun,&nbsp;Meijuan Zou,&nbsp;Hongyu Piao","doi":"10.1208/s12249-025-03118-3","DOIUrl":"10.1208/s12249-025-03118-3","url":null,"abstract":"<div><p>Psoriasis is a systemic immune disease with severe inflammation and skin thickening. Roflumilast (ROF) blocks cAMP hydrolysis, and paclitaxel (PTX) inhibits cell proliferation; both are effective in topical psoriasis treatment. However, the combination of ROF and PTX has not been reported. This study explored their synergistic mechanism and formulated a ROF-PTX oleogel with strong skin adhesion, low viscosity, enhanced skin penetration, and increased retention. The oleogel, prepared via direct gelation with jojoba oil as oil phase, PPG-15 as solvent, Transcutol as solubilizer, and hydrogenated castor oil as oleogelator. It showed 78.9% holding oil capacity and a viscosity of 0.4049 Pa·s, indicating excellent stability and adhesion. In the imiquimod-induced psoriasis model, the ROF:PTX (1:1) oleogel reduced Baker scores and splenic indices more effectively than ROF or PTX alone. Histological studies suggested that the combination was superior in reducing inflammation and skin thickening. The ROF:PTX (1:1) oleogel group exhibited lower Baker scores and epidermal thickness, demonstrating superior therapeutic efficacy. The H-SCORE revealed a 2.95-fold reduction in IL-17 levels compared to the model group, highlighting the potential of the ROF and PTX combination as an effective psoriasis treatment strategy.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925630","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":"Leveraging Nanoscience and Strategic Delivery for the Expedition of Osteoporosis","authors":"Pramoda G,&nbsp;Rahul K. Verma,&nbsp;Rahul Shukla","doi":"10.1208/s12249-025-03120-9","DOIUrl":"10.1208/s12249-025-03120-9","url":null,"abstract":"<div><p>Osteoporosis is a globally affecting bone disease characterized by reduced bone mineral density, in which women are more insidious to the disease. It accounts for 8.9 million fractures annually, and about 50% of repeated hip fractures cause permanent disabilities. With the knowledge of determinants and pathology, various FDA-approved drugs and therapies are available for the management of the disease, but the challenges associated with those therapies lead to the adoption of nanotechnology in osteoporosis management. The nanosystems developed for the management of osteoporosis are nanogenerators, nanobubbles, microneedles, nanogels, implantable delivery systems, nanoparticles, nanofibrous scaffolds, and nanocements that probably address the current challenges related to the diagnosis and cure. In view of targeted accumulation of the cargo, various moieties assisted the nanocarrier system for selective distribution to bone, and the development of different types of nanotechnology-based delivery systems has been briefed in this review.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of Chitosan Nanoparticles Containing Quercetin-β-Cyclodextrin Inclusion Complex for Improved Solubility, Brain Targeting, and Neuroprotective Potential Against Epilepsy","authors":"Priyabrata Pradhan,&nbsp;Vineet Kumar Rai,&nbsp;Jitu Halder,&nbsp;Durgamadhab Kar,&nbsp;Shakti Ketan Prusty,&nbsp;Saroj Kumar Rout,&nbsp;Salim Manoharadas,&nbsp;Subramanian Palanisamy,&nbsp;Priyanka Dash,&nbsp;Chandan Das,&nbsp;Biswakanth Kar,&nbsp;Goutam Ghosh,&nbsp;Goutam Rath","doi":"10.1208/s12249-025-03119-2","DOIUrl":"10.1208/s12249-025-03119-2","url":null,"abstract":"<div><p>The present study focuses on developing and optimising chitosan nanoparticles containing quercetin-β-cyclodextrin inclusion complex (QNPs) using the nanoprecipitation method to enhance quercetin's solubility, stability, and bioavailability. A comprehensive optimization study revealed that Batch B6, which utilized ethanol as the solvent, poloxamer 188 as the stabilizer, and chitosan at a concentration of 0.2% (w/v), exhibits optimal characteristics required for providing a stable colloidal system. The prepared nanoparticles were characterized for their physicochemical properties using FTIR, DSC, X-ray Diffraction, and SEM, which confirmed the successful inclusion of quercetin within the β-cyclodextrin complex and the reduction in crystallinity. <i>In-vitro</i> drug release studies demonstrated a controlled release profile for QNPs compared to free quercetin and the inclusion complex. Pharmacokinetic evaluation in mice via oral administration revealed a significant enhancement in systemic circulation and brain uptake, with QNPs showing a peak plasma concentration of 6.5 µg/mL at 2 h and a brain concentration of 3.5 µg/g at 4 h, indicating improved bioavailability and prolonged retention. In the Pentylenetetrazole and Kainic acid-induced epilepsy mice model, QNP significantly reduced seizure duration, frequency of seizures, and severity scores favoured the QNP formulation over free quercetin. QNPs also exhibited a significant neuroprotective effect by enhancing antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione reductase in brain tissue. Furthermore, Na⁺/K⁺-ATPase activity was significantly preserved in QNP-treated groups, indicating membrane stability and reduced neuronal excitability. These findings suggest that QNPs offer a promising strategy for enhancing quercetin's therapeutic efficacy in neurological disorders such as epilepsy.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"26 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913838","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}