Assay and drug development technologies最新文献

{"title":"Antiangiogenic Effect of <i>Pluchea lanceolata</i> in Adjuvant-Induced Rheumatoid Arthritis in Wistar Rats by Downregulating VEGF Signaling Pathway and Proinflammatory Cytokines.","authors":"Nimesh Bhardwaj, Praveen Kr Dixit, Kandasamy Nagarajan, Snigdha Bhardwaj","doi":"10.1177/1540658X261472169","DOIUrl":"https://doi.org/10.1177/1540658X261472169","url":null,"abstract":"<p><p><i>The current work aimed to investigate the therapeutic potential of</i> Pluchea lanceolata <i>(Rasna) in the management of rheumatoid arthritis (RA) using</i> in silico, in vitro, <i>and</i> in vivo <i>studies. After administering Rasna (aqueous and ethanolic extracts), physical parameters such as paw volume and arthritic score were found suppressed in rats (in Freund's complete adjuvant-induced model). Also, radiography and histopathological findings revealed that joint deformities, pannus formation, and tissue swelling of the ankle joint improved when compared with standard and arthritis-induced after 4 weeks. Simultaneously, ELISA results revealed that the serum levels of IL-1β, IL-6, TNF-α, C-reactive protein (CRP), and COL2A1 were lowered when compared with the standard group. An</i> in silico <i>study revealed that quercetin, isorhamnetin, and linalool were the potential active phytoconstituents and showed promising binding affinity toward targets such as KDR (VEGFR2), matrix metalloproteinase (MMPs), ALOX5, IL-1β, IL-6, TNF-α, CRP, and COL2A1. The biological mechanism of Rasna includes several molecular and cellular functions involving the downregulation of angiogenesis through the vascular endothelial growth factor signaling pathway, the MAPK signaling pathway, PI3K-Akt signaling pathway, and the reduction of cytokines and anti-collagen II antibodies. Rasna inhibits the activation of the abovementioned pathways and mRNA expression of IL-1β, IL-6, and TNF-α in RA. The study suggested the potential use of Rasna in managing arthritis treatment over the conventional therapy in immunocompromised patients.</i></p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261472169"},"PeriodicalIF":1.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787689","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":"Comprehensive Physicochemical Characterization and Release Kinetics of an Astaxanthin Nanoplex: Integrated <i>In Silico</i> and <i>In Vitro</i> Evaluation.","authors":"Manish Arora, Chetna Hemrajani, Anshul Jamwal, Vikrant Dalwal, Rohit Sharma, Darsh Gautam, Somdutt Mujwar, Thakur Gurjeet Singh, Poonam Negi","doi":"10.1177/1540658X261429239","DOIUrl":"10.1177/1540658X261429239","url":null,"abstract":"<p><p>\u0000 <i>Astaxanthin (AST) is a potent xanthophyll carotenoid that is well known for its extraordinary therapeutic and antioxidant properties. However, its weak water solubility and low bioavailability limit its application in pharmaceuticals. The present study aimed to enhance the solubility, stability, and sustained release of AST by developing an AST-chitosan (AST-CHT) nanoplex via green polyelectrolyte complexation. The nanoplex was lyophilized to obtain a stable dry powder and systematically characterized for its physicochemical properties. Comprehensive evaluations, including particle size analysis, entrapment efficiency, zeta potential, Fourier-transform infrared spectroscopy, powder X-ray diffraction, differential scanning calorimetry, and transmission electron microscopy, confirmed successful nanoplex formation with improved solubility and amorphous transformation. Molecular docking studies revealed stable electrostatic and hydrophobic interactions between AST and CHT, thereby supporting the complex's stability. The optimized formulation, F5 (AST:CHT = 1.48:1% w/w), was selected based on its high entrapment efficiency (71.8%), appropriate particle size (420.1 nm, polydispersity index of 0.465), drug loading (0.79), and moderate zeta potential (-12.87 mV), which together ensured optimal stability and sustained release performance. <i>In vitro</i> release studies indicated sustained release following zero-order and Korsmeyer-Peppas kinetics (correlation coefficient of 0.9759). Stability analysis confirmed stability for 2 months. Overall, the developed AST-CHT nanoplex offers a promising, eco-friendly, and mechanistically supported nanodelivery system for improving the therapeutic performance and bioavailability of AST.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"461-475"},"PeriodicalIF":1.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040942","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":"Formulation, Characterization, and Biological Assessment of Embelin-Loaded Glycerosomes.","authors":"Monika Dhaka, Md Habban Akhter, Maha Alsunbul","doi":"10.1177/1540658X261449845","DOIUrl":"10.1177/1540658X261449845","url":null,"abstract":"<p><p>\u0000 <i>Despite embelin's (EB) promising biological activities including the hepatoprotective effect, its clinical use is constrained by inadequate solubility and low oral bioavailability, which restrict its therapeutic effectiveness. The current study aimed to address this gap by developing EB-loaded glycerosomes (GLSMs), an advanced vesicular system designed to improve oral bioavailability and enhance drug delivery to the liver. EB-loaded GLSMs were prepared using a thin-film hydration method and optimized via a 3² Box-Behnken design. The concentrations of soy lecithin and glycerol, along with the probe sonication cycle, were chosen as independent variables to study their effect on vesicle size and percentage drug entrapment. The prepared formulation was tested for vesicle size and its distribution, surface charge (zeta potential), and drug release and was also assessed <i>in vivo</i>. The optimized formulation exhibited a vesicle size of 214.41 ± 2.12 nm, a polydispersity index of 0.145 ± 0.02, a zeta potential of -30 ± 1.14 mV, and an entrapment efficiency (EE) of 94.74% ± 0.056%. Transmission electron microscopy images confirmed the presence of uniform, spherical vesicles with no signs of aggregation. The sustained-release properties of the GLSM formulation were evident, with 99% of EB released from the pure drug suspension within 2 h, compared with the same amount released from the EB-loaded GLSMs over 12 h. <i>In vivo</i> pharmacokinetic studies showed a significantly higher plasma maximum concentration (C_max), AUC_0-t, and AUC_0-∞ values for optimized EB-loaded GLSMs compared with aqueous EB suspension (<i>p</i> < 0.01), resulting in approximately 2.5-fold greater plasma bioavailability. Furthermore, rats treated with the optimized EB-loaded GLSMs showed significantly lower serum triglyceride and total cholesterol levels compared with those treated with the aqueous EB suspension. The developed EB-loaded GLSMs exhibited promising lipid-lowering and hepatoprotective effects, suggesting their potential as a therapeutic approach for liver diseases.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"493-510"},"PeriodicalIF":1.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263007","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":"Ellagic Acid-Loaded Microsponges Impregnated Chitosan-Guar Gum Hydrogel for Wound Therapy: Investigation on Rheology, Antioxidant, and Antimicrobial Activities.","authors":"Manjeet Dahiya, Anroop B Nair, Varsha Kadian, Ahmed S Alnaim, Shery Jacob, Bandar Aldhubiab, Rashed M Almuqbil, Rekha Rao","doi":"10.1177/1540658X261447032","DOIUrl":"10.1177/1540658X261447032","url":null,"abstract":"<p><p><i>The therapeutic efficacy of ellagic acid could be improved by developing suitable carrier system. The present research was to develop ellagic acid-loaded microsponges impregnated with chitosan-guar gum hydrogel and evaluate its potential as novel carrier system for wound therapy. Ellagic acid-loaded microsponges were fabricated using ethyl cellulose by the quasi-emulsion solvent diffusion method and incorporated into chitosan and guar gum hydrogel. Prepared microsponges were found to be spherical, non-aggregated particles ranging in size from 100 to 300 µm. The hydrogel formulation was assessed for pharmaceutical characteristics, rheology, drug release, antioxidant and antimicrobial activities. FTIR confirmed that the bioactive and the excipients used are chemically compatible. Spreadability data confirm precise and easy dosage application of microsponge hydrogel in the skin. Results of rheological studies revealed that microsponge-loading considerably increased elastic strength, while frequency and temperature sweep tests demonstrated viscoelastic stability at 25°C. A sustained ellagic acid release for 12 h following the Higuchi kinetics model (<i>R</i>² = 0.987) was noticed with microsponge loaded chitosan-guar gum hydrogel. The good antioxidant activity exhibited at doses (50-100 µg/mL) by the developed hydrogel implies that the formulation successfully preserves bioactive antioxidant properties. Developed hydrogel retained antimicrobial activity against the test organisms and showed notable inhibition against <i>Pseudomonas aeruginosa</i> at low concentration (12.5 µg/mL). This study establishes an effective topical formulation of ellagic acid-loaded microsponges with potential antioxidant and antimicrobial efficacy, highlighting its possibility to be used for wound healing</i>.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"476-492"},"PeriodicalIF":1.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810208","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":"Formulation and Optimization of Chitosan-Based Flurbiprofen Nanoparticles for Ocular Delivery: A Design of Experiments Approach.","authors":"Emine Dilek Özyılmaz","doi":"10.1177/1540658X261429252","DOIUrl":"10.1177/1540658X261429252","url":null,"abstract":"<p><p>This study aimed to design and develop flurbiprofen-loaded chitosan nanoparticles for ophthalmic drug delivery, with the objectives of enhancing formulation stability, sustaining drug release, and improving patient comfort. This study introduces an optimized chitosan-based nanoparticle system for ocular delivery of flurbiprofen, achieving high encapsulation efficiency, physiological compatibility, and sustained release for 20 h. The findings demonstrate a practical, patient-friendly approach that enhances drug bioavailability and stability compared with conventional eye drops. Flurbiprofen-loaded nanoparticles were prepared using gelation and optimized through a Box-Behnken design. The influence of formulation variables (0.1%-0.3% w/v chitosan concentration, 0.2-0.6 mL/min dropping rate, and 500-900 rpm mixing speed) was assessed. The optimized nanoparticles were evaluated for particle size, polydispersity index (PDI), zeta potential, pH, osmolarity, and entrapment efficiency (%). The optimized formulation was achieved at 0.2% (w/v) chitosan concentration, a dropping rate of 0.4 mL/min, and a mixing speed of 700 rpm. The nanoparticles exhibited a particle size of 110.0 ± 2.20 nm, PDI of 0.347 ± 0.03, and zeta potential of + 15.4 ± 3.8 mV. The entrapment efficiency was 80.89%. The formulation was adjusted to physiological conditions (pH 6.7, osmolarity 300 mOsm/kg). <i>In vitro</i> studies showed a controlled release of flurbiprofen over 20 h. The optimized chitosan-based nanoparticle system demonstrated favorable physicochemical stability, high encapsulation efficiency, and sustained release of flurbiprofen. Compared with conventional ocular formulations, this structured nanoparticle delivery system offers superior drug retention and extended therapeutic action.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"444-454"},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455374","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":"Molecular Mechanism of μ-Opioid Receptor Activation.","authors":"Yuhan Qu, Fuming Liu","doi":"10.1177/1540658X261442281","DOIUrl":"10.1177/1540658X261442281","url":null,"abstract":"<p><p>This study demonstrates through an integrated computational and experimental approach that classical calcium channel blockers (CCBs) from four distinct structural classes possess previously unrecognized Mu-opioid receptor (MOR) activation capabilities. Virtual screening revealed stable binding modes between the investigated compounds (verapamil, cinnarizine, diltiazem, and flunarizine) and the 7SBF protein target, with cinnarizine exhibiting the most favorable interaction profile through strong hydrogen bonding with TYR-236 and GLN-124. Molecular dynamics simulations confirmed binding stability, particularly for cinnarizine, which maintained a root-mean-square deviation below 0.3 nm. Experimental validation via cAMP inhibition assays demonstrated significant MOR activation by all compounds, with cinnarizine showing superior potency (IC₅₀ = 21.4 ± 1.5 nM) and efficacy (Imax = 70% ± 2%). The conserved MOR activation across structurally diverse CCBs supports a polypharmacological mechanism where these drugs concurrently modulate both calcium channels and opioid receptors. These findings not only elucidate a novel aspect of CCB pharmacology but also suggest new avenues for drug repurposing and the development of multi-target cardiovascular therapeutics.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"431-443"},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716149","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":"Indolizine Compound Selection for HPV Anticancer Active Prediction Using CNN Classifier with ADME Descriptors.","authors":"Sangeeta Mahaur, Sukirti Upadhyay","doi":"10.1177/1540658X261429312","DOIUrl":"10.1177/1540658X261429312","url":null,"abstract":"<p><p>\u0000 <i>Despite the significant progress made in developing different <i>in silico</i> methodology for structure activity research over the past few decades. The ability to predict correlation structure activity (CSA) from absorption distribution metabolism excretion (ADME) descriptors to select indolizine compounds for human papilloma virus (HPV) anticancer activity continues to pose a challenge. This study employed five machine learning (ML) algorithms for classification, viz., stochastic gradient descent (SGD), random forest (RF), support vector machine (SVM), convolutional neural network (CNN), and logistic regression (LR), to perform the classification based on ADME-related physiochemical descriptors of 8,900 indolizine compounds to predict the CSA. The present study focuses on 26 well-known parameters to optimize the results, which are utilized for ML models SGD, RF, SVM, CNN, and LR for classification. The CNN achieved the best results with the highest overall accuracy and average loss values of 98.33% and 0.16, respectively. On the other hand, the SGD, RF, SVM, and LR recorded the accuracy values of 95.32%, 93.23%, 96.03%, 94.03%, and loss values of 0.046, 0.067, 0.039, and 0.059, respectively. It is stated that from the obtained results, the CNN is performing better compared to other methods. The cross-validation and results are done with the relationship of descriptors, viz., accuracy, correlation, distribution, area under the receiver operating characteristic, area under the precision recall curve, and bootstrap error analysis. This study demonstrated the utility of ML to facilitate early prediction of indolizine compounds for HPV anticancer activity in preclinical development.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"24 5","pages":"381-413"},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040920","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":"Tongnao Decoction Exerts a Treatment Effect on Ischemic Stroke by IL-6/PI3K/Akt/GSK-3β Pathway: Based on the Network Pharmacology and Molecular Docking.","authors":"Jiale Gan, Yujun Cong, Lulu Li, Fei Ma, Xinyi Yang, Yongxing Deng, Yan Liu, Yang Wu, Hui Jiang, Zhaoyao Chen, Wenlei Li, Yuan Zhu, Minghua Wu","doi":"10.1177/1540658X261438876","DOIUrl":"10.1177/1540658X261438876","url":null,"abstract":"<p><p>Ischemic stroke (IS) is an important disease leading to high disability and mortality, and the current clinical treatment is limited. Tongnao Decoction (TND) is a traditional Chinese herbal formula for treating IS, but its pharmacological mechanism remains unclear. This study aims to elucidate the molecular mechanism through network pharmacology, molecular docking, and related experimental verification. First, the bioactive components of TND, along with their potential targets and IS-related gene targets, were identified through multiple databases. Subsequently, an \"herb-active component-disease gene target\" network and a protein-protein interaction (PPI) network were constructed. Combined with enrichment analysis, key biological processes and signaling pathways were identified. Following this, molecular docking experiments were conducted to preliminarily validate drug-target interactions. Finally, the efficacy of the relevant pathway targets was validated in a photochemically induced mouse cerebral ischemia model. A total of 90 active compounds and 615 target genes were screened. PPI network analyses suggested that TP53, EGFR, STAT3, AKT1, and IL-6 were the hub targets. TND significantly modulates inflammatory biological processes and the PI3K-Akt signaling pathway during IS treatment. Molecular docking analysis indicated that the primary components of TND may exhibit favorable binding affinity to multiple hub target proteins, including TP53, EGFR, STAT3, AKT1, and IL-6. Further <i>in vivo</i> experiments showed that TND dramatically improved neurological function, reduced neuronal damage, and decreased IL-6 expression in brain tissue. In addition, TND stimulated the PI3K/Akt/GSK-3β pathway. These findings imply that TND and its key bioactive components, coryincine, dihydrocapsaicin, and 4 (4'-hydroxybenzyloxy)benzyl methylether exert therapeutic effects on IS through the IL-6/PI3K/Akt/GSK-3β pathway.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"414-430"},"PeriodicalIF":1.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627032","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":"Decoding Cholesterol Metabolic Regulation by Naotai Formula in Stroke Management: An Integrated Network Pharmacology and Mendelian Randomization Approach.","authors":"Haiwei Jiang, Chang Gao, Dan Wang, Hao Tian, Bifeng Zhu","doi":"10.1177/1540658X261415762","DOIUrl":"10.1177/1540658X261415762","url":null,"abstract":"<p><p>Naotai formula (NTF) is clinically used for stroke treatment, yet its molecular mechanisms involving vascular and metabolic regulation remain unclear. This study combines network pharmacology (NP) and Mendelian randomization to explore NTF's therapeutic targets and pathways in stroke. Stroke-related genes were sourced from public databases, and NTF's active compounds were screened using SwissADME. Summary-data-based Mendelian randomization (SMR) analysis, combined with colocalization, integrated stroke genome-wide association study data with blood expression quantitative trait loci and protein quantitative trait loci datasets to identify genes/proteins causally linked to stroke risk. Protein-protein interaction (PPI) network and drug-compound-target networks were constructed using Cytoscape and R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified functional roles. Molecular docking assessed interactions between key compounds and prioritized targets. A total of 579 overlapping genes linked NTF and stroke. SMR identified 44 stroke-associated genes, with vascular endothelial growth factor A, angiotensinogen (AGT), and lipoprotein(a) replicated. Validation in Brain-eMeta supported eight of these targets, supporting tissue relevance. Enrichment analyses highlighted pathways including PPAR signaling, cholesterol metabolism, and vascular function. Core targets (Adiponectin, C1Q and collagen domain containing (ADIPOQ), Scavenger Receptor Class B Member 1 (SCARB1), and AGT) emerged from PPI networks. Molecular docking confirmed strong binding between NTF's Calycosin and AGT, a key renin-angiotensin system protein. NTF likely mitigates stroke by modulating genes involved in cholesterol metabolism and vascular regulation. The predicted Calycosin-AGT interaction provides a genetically informed hypothesis for a possible role in renin-angiotensin modulation. This integrative approach provides genetic and mechanistic insights into NTF's therapeutic efficacy.</p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"281-295"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028248","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":"A Nasal Hydrogel Combining Metformin and Curcumin for Potential Nose-to-Brain Therapy in Neurodegenerative Disorders.","authors":"Emine Dilek Özyılmaz","doi":"10.1177/1540658X261429259","DOIUrl":"10.1177/1540658X261429259","url":null,"abstract":"<p><p>\u0000 <i>Neurodegenerative disorders such as Alzheimer's and Parkinson's disease remain a significant therapeutic challenge due to the restrictive nature of the blood-brain barrier (BBB) and the limited efficacy of current pharmacological treatments. Intranasal administration has emerged as a promising noninvasive strategy that enables direct drug delivery to the brain by bypassing the BBB. This study aimed to design and optimize a dual-drug nasal hydrogel containing metformin hydrochloride, a hydrophilic AMP-activated protein kinase activator, and curcumin, a lipophilic antioxidant and anti-amyloid agent, and to provide synergistic neuroprotection. The formulation was prepared using carbopol as the gel matrix and characterized in terms of physicochemical stability, drug content uniformity, rheology, <i>in vitro</i> release, and excipient compatibility. A Box-Behnken design was used to systematically evaluate the effects of carbopol, glycerin, and curcumin concentrations on critical quality attributes. The optimized hydrogel exhibited acceptable pH, viscosity suitable for nasal administration, and sustained biphasic drug release with a cumulative 6-h release of approximately 85% for metformin and 39% for curcumin according to the Higuchi drug release model (<i>R</i>² > 0.98). Collectively, these results highlight the feasibility of an integrative intranasal hydrogel platform to overcome the bioavailability challenges of both agents. The proposed system offers a patient-friendly, noninvasive approach for potential nose-to-brain therapy in neurodegenerative disorders and warrants further preclinical and <i>in vivo</i> investigation.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"323-333"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389122","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}