Search Results (2,352)

Curcumin exhibits potent anti-obesity and anti-inflammatory activities; however, its therapeutic application is limited by poor aqueous solubility and low oral bioavailability. A curcumin-loaded chewable gel was developed to transform into an in situ gastric gel upon contact with gastric fluid after mastication. Curcumin solid dispersions (CUR-SDs) were prepared with Eudragit^® EPO (1:1–1:7, w/w) using the solvent evaporation method. The optimized formulation (1:3) markedly enhanced solubility and dissolution in acidic medium (0.1 N HCl, pH 1.2) compared with crystalline curcumin and physical mixtures. The optimized CUR-SD was subsequently incorporated into chewable gels composed of sodium alginate and κ-carrageenan, with calcium carbonate as a gas-forming agent. The formulations formed buoyant matrices under acidic conditions, exhibiting floating lag times of 21–215 s and sustaining drug release for up to 8 h. Increasing polymer content improved mechanical strength and modulated release kinetics. Among the tested formulations, F7 achieved the optimal balance between texture properties, floating behavior, and controlled-release performance. In LPS-stimulated RAW264.7 macrophages, curcumin, CUR-SD, and F7 showed comparable and potent anti-inflammatory activity (IC₅₀ = 4.12–4.84 µg/mL), outperforming indomethacin. In 3T3-L1 adipocytes, F7 significantly reduced lipid accumulation (~47%) in a concentration-dependent manner. These findings demonstrate that this transformable chewable in situ gelling platform is a promising gastroretentive strategy for improving the oral therapeutic efficacy of poorly soluble bioactive compounds for anti-obesity applications. Full article

The bioactive compounds in thyme essential oil (TEO) have been investigated as natural preservatives. However, their direct application in foods is limited by their poor water solubility and high volatility. In this context, nanoemulsions represent promising delivery systems for bioactive compounds due to their improved physicochemical stability and functional performance. This study aimed to develop and characterize TEO nanoemulsions prepared by ultrasound-assisted encapsulation using an ultrasonic probe and whey protein concentrate as a surfactant, with potential application in chicken burgers. Different sonication times (1, 3, 5, 7, and 10 min) were evaluated, and ultrasonication time was evaluated as the experimental variable. The formulation processed for 3 min presented the smallest hydrodynamic diameter (289 nm) and a homogeneous spherical morphology. The nanoemulsions showed low cytotoxicity, maintaining cell viability above 90% at all evaluated concentrations. In vitro antibacterial assays demonstrated activity against Staphylococcus aureus and antifungal effects against Aspergillus and Penicillium species. When applied to chicken burgers, the treatment containing 100 ppm of nanoencapsulated TEO contributed to reductions in S. aureus and mesophilic aerobic microorganism counts during 7 days of refrigerated storage. These findings indicate that TEO nanoemulsions present potential as natural antimicrobial systems for food preservation applications. Full article

Bovine viral diarrhea virus (BVDV), a globally persistent pathogen, causes bovine viral diarrhea-mucosal disease (BVD-MD), a contagious bovine disease posing significant pressures on both public health and economic development. Baicalin (BA), a flavonoid derived from Scutellaria baicalensis, exhibits broad antiviral activities but suffers from poor aqueous solubility and low bioavailability, limiting its therapeutic potential against BVDV. To address this limitation, we developed BA-loaded poly (ethylene gly-col)-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (BA-PEG-PLGA NPs). While autophagy and NLRP3 inflammasome activation have been individually implicated in viral pathogenesis, their functional crosstalk during BVDV infection remains uncharacterized. Herein, we evaluated the antiviral efficacy of BA-PEG-PLGA NPs through integrated in vitro and in vivo experiments. We employed quantitative polymerase chain reaction (qPCR), transcriptome sequencing, Western blot analysis, immunofluorescence microscopy, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) to investigate the mechanisms by which BA and BA-PEG-PLGA NPs combat bovine viral diarrhea virus (BVDV) infection. We found that both free BA and BA-PEG-PLGA NPs effectively attenuated BVDV replication in vitro and in vivo; notably, the nano-formulation exhibited superior efficacy. Mechanistically, BA and its nano-formulation restored autophagy homeostasis, suppressed ROS overproduction, and blocked NLRP3 inflammasome activation and pyroptotic cell death effects comparable to the specific NLRP3 inhibitor MCC950. These findings establish the autophagy–NLRP3/pyroptosis axis as a critical pathogenic mechanism in BVDV infection and reveal that nano-formulated baicalin represents an antiviral strategy by coordinately targeting this axis. This work not only provides a translatable nanomedicine approach for BVDV control but also expands the mechanistic understanding of flavonoid-based interventions in viral inflammatory diseases. Full article

Background: Dengue virus (DENV) does not have any effective antiviral therapy. The Cinnamomum verum has cinnamic acid and oleic acid that could inhibit important viral proteins. Aim: To compare their inhibitory capacity with the key DENV proteins through molecular docking, molecular dynamics and in silico ADMET. Methods: Phytochemical profiling of the ethanolic extract of the bark was done by GCMS. AutoDock Vina (version 1.2.0) was used to dock cinnamic acid and oleic acid to key proteins of DENV (NS5, NS3, and envelope) in the presence of ribavirin as the reference. The best complexes were then subjected to 50 ns of molecular dynamics simulation and stability measured by RMSD, RMSF, Rg, SASA, hydrogen bonding and RDF. Validated in silico tools were used to predict the ADMET properties. Results: Analysis of GC–MS revealed cinnamic acid (85.92%) and oleic acid (5.33%). The outcome of docking was that the cinnamic acid had the greatest affinity with NS5 (−5.970 kcal/mol) and the capsid protein (−5.755 kcal/mol), and oleic acid showed the highest affinity with the capsid (−6.150 kcal/mol) and then with NS5 (−5.209 kcal/mol). Both ligands had a relatively weak interaction with NS3. Simulation of the molecular dynamics showed the stability of the top complexes, especially the cinnamic acid–NS5 complex, that retained low RMSD (1.6–1.9 A), stable Rg and SASA profiles, and continued hydrogen bonding during the 50 ns period. The use of cinnamic acid in ADMET projections was more preferable, as it was more soluble, orally bioavailable (0.91), and drug-like (QED 0.65), but oleic acid revealed higher lipophilicity and lower drug-like properties (QED 0.29). Conclusions: Cinnamic acid showed specificity towards the NS5 proteins with the help of stable dynamics and good predicted pharmacokinetics, which are features that make it a promising multi-target anti-DENV scaffold. Oleic acid exhibited poor affinity and poor pharmacokinetic properties. The findings are predictive and must be validated using biochemical, cellular, and toxicological means to prove the antiviral efficacy and safety. Full article

Polyethylene terephthalate (PET) waste accumulation requires sustainable recycling alternatives. While Ideonella sakaiensis PETase offers a green solution, its industrial application is hindered by low solubility and poor thermostability. In this study, we systematically evaluated the synergistic effects of maltose-binding protein (MBP) fusion and periplasmic translocation strategies to optimize PETase production in Escherichia coli. Our results demonstrate that MBP acts as a potent solubilizing partner for PETase, with the cytosolic MBP–PETase variant achieving a high purification yield of 8.4 mg per gram of wet cell weight–a significant improvement over the PelB–PETase control (1.1 mg per gram of wet cell weight). Furthermore, the periplasmic MalE–MBP–PETase construct provided an optimal intermediate compromise between the yield, thermal stability, and catalytic activity by leveraging the oxidative environment of the periplasm for critical disulfide bond formation. Although PelB–PETase exhibited higher specific activity, its low yield limits industrial scalability. This study establishes a robust plug-and-play platform for high-throughput PET depolymerization, providing a foundational step toward a circular plastic economy. Full article

Osteosarcoma (OS), the most common primary malignant bone tumor in children and young adults, is characterized by aggressive behavior, frequent metastasis, and resistance to chemotherapy, resulting in poor clinical outcomes. Increasing evidence indicates that OS progression is not solely driven by tumor-intrinsic factors but is strongly influenced by dynamic interactions within the tumor microenvironment (TME). This literature review synthesizes current research on the roles of endothelial cells, fibroblasts, mesenchymal stromal cells, immune populations, and osteoclasts in OS pathogenesis, with emphasis on cell–cell interactions mediated by direct contact, soluble factors, and extracellular vesicles. The studies demonstrate that these interactions promote tumor proliferation, immune evasion, extracellular matrix remodeling, metastatic dissemination, and therapeutic resistance. Adaptive responses of both tumor and stromal cells to environmental stressors contribute to chemoresistance and disease progression. Collectively, our findings highlight the multifactorial nature of OS driven by complex cellular crosstalk within the TME. Understanding these mechanisms highlights the limitations of conventional chemotherapy and encourages the development of combined therapeutic approaches, including targeted therapies, immunomodulation, and microenvironmental interventions. Continued investigation into tumor–microenvironment interactions may facilitate the identification of actionable targets and improve personalized treatment approaches for OS. Full article

Polyphenols, abundant compounds found in natural sources, exhibit various biological activities, including immunomodulatory properties that can either stimulate or suppress immune responses, making them promising for therapeutic applications. However, their poor solubility, low bioavailability, rapid metabolism, and non-specific distribution require advanced drug delivery strategies to overcome limitations in clinical translations. Therefore, nano-drug delivery systems have been intensively studied to explore the full therapeutic potential of polyphenols. Distinct from conventional paradigms where polyphenols serve solely as active compounds, this review advances the concept of polyphenol-based nanomedicine as dual-functional platforms: bioactive structural components and intrinsic immune modulators. Recent strategies to improve the loading efficacy of polyphenols, enhance their cellular uptake, prolong circulation, and enhance specific delivery based on those nanocarriers are emphasized. In addition, polyphenol-based nanoparticles, in which polyphenols serve as structural components, were also studied as self-therapeutics or multifunctional nanocarriers for drug delivery. We intensively focus on their immunomodulatory applications and highlight their potential in preclinical as well as clinical settings for the treatment of various diseases and therapeutic purposes, including autoimmune diseases, cancer immunotherapy, vaccination, inflammation, and infectious diseases. Although polyphenol nanoparticle development has made significant advances, there remain challenges in formulation stability, unclear in vivo toxicity profiles, and clinical translation. Further studies on optimizing nanoparticle design and assessing long-term toxicity are necessary to materialize their application. A combination of polyphenol nanoparticles with other immunotherapies may promise a pronounced efficacy and safety profile. Full article

Terpenoids represent a large class of bioactive natural compounds with promising pharmacological properties, including anti-inflammatory, antimicrobial, and anticancer activities. However, their clinical application is often limited by poor aqueous solubility, low membrane permeability, and suboptimal bioavailability. Phytosomal delivery systems have emerged as a promising strategy to enhance the pharmacokinetic performance of plant-derived compounds by forming molecular complexes between bioactive molecules and phospholipids. This review critically examines the structural principles, preparation methods, physicochemical characterization, and biological performance of terpenoid phytosomes. Particular attention is given to the molecular interactions between terpenoids and phospholipids that govern complex formation and vesicular assembly. The review also summarizes current analytical techniques used to confirm phytosome formation and discusses the influence of formulation parameters, including phospholipid composition and molar ratios, on stability and biological activity. In addition, emerging insights from molecular modeling and membrane interaction studies are considered to better understand the mechanisms underlying improved drug delivery. Finally, challenges related to safety assessment, manufacturing scalability, and clinical translation of phytosomal systems are discussed. Overall, terpenoid phytosomes represent a promising nanodelivery platform capable of improving the pharmacokinetic profile and therapeutic potential of terpenoid compounds. Full article

Poor aqueous solubility remains a major limitation for the oral delivery of many active pharmaceutical ingredients (APIs). Deep eutectic solvents (DESs) exhibit remarkable drug-solubilization capacity, yet rapid precipitation upon aqueous dilution can compromise their ability to sustain supersaturation. This study investigates polymer-embedded DES (PEDES) systems as liquid supersaturating drug delivery platforms in which hydration and polymer chemistry jointly govern thermodynamic solubilization and kinetic stabilization. A choline chloride/DL-malic acid DES was prepared with 5% or 15% (w/w) water and combined with polyvinylpyrrolidone (PVP) or polyacrylic acid (PAA). Griseofulvin (GRF) was used as a precipitation-prone model drug. Structural characterization (ATR-FTIR, ¹H-NMR), equilibrium solubility measurements, storage stability studies, and non-sink dissolution testing were conducted to elucidate formulation behavior. The DES systems enhanced GRF solubility by up to ~59-fold relative to phosphate buffer (PBS, pH 6.8). Polymer incorporation produced hydration- and concentration-dependent effects. These results suggest the presence of competitive or cooperative interaction regimes. At 5% water, PEDES formulations failed to prevent recrystallization and showed limited supersaturation maintenance. In contrast, PEDES systems containing 15% water exhibited improved stability, with the formulation containing 4% PAA sustaining elevated drug concentrations for 120 min under non-sink conditions. Low-frequency solution-state ¹H-NMR confirmed stronger GRF–PAA interactions relative to PVP, supporting the role of polymer–drug association in supersaturation stabilization. These findings demonstrate that PEDES performance emerges from a hydration-dependent balance between solvent structuring and drug–polymer interactions, highlighting hydration and polymer functionality as key parameters for the rational design of liquid supersaturating systems. Full article

Background: Circulating cytokines and their soluble receptors in body fluids have been implicated in the pathogenesis of multiple sclerosis (MS). Alterations in serum levels of pro- and anti-inflammatory cytokines and/or their soluble receptors can dysregulate central nervous system (CNS) signaling pathways and, therefore, may serve as potential biomarkers for the diagnosis of MS. Therefore, the primary end-point of this study is to investigate the utility of various cytokines and their soluble receptors as diagnostic biomarkers in MS. The secondary outcome is also to assess whether these cytokines are useful in differentiating the severity of MS. Methods: In this case–control study, we compared a panel of pro-inflammatory interleukins (ILs), including IL18 and tumor necrosis factor-alpha (TNFα), soluble IL receptors (sIL7Rα and sIL2Rα), and insulin-like growth factor-1 (IGF-1) in 45 MS patients and in 45 healthy control individuals matched for sex and age. Associations of these biomarkers with age, disease severity (Expanded Disability Status Scale [EDSS]), disease duration, and age at first MS symptom onset were also assessed. Results: Serum levels of cytokines and soluble IL receptors were elevated in MS patients compared to healthy controls. IGF-1 was lower (p < 0.001) in the MS patients than in the healthy individuals. The serum level of IGF-1 was higher (p < 0.01) in the remitting-relapsing phase compared to the primary progression and secondary progression stages. Similarly, only IGF-1 was more elevated (p < 0.01) in the mild stage compared to the moderate stage based on the EDSS score. Receiver operating characteristic (ROC) curve analysis demonstrated that IL18 had excellent discriminatory power for the diagnosis of MS (p < 0.001), with an area under the curve (AUC) of 0.96 ± 0.017, followed by IGF-1 (p < 0.001), which showed strong diagnostic performance (AUC = 0.873 ± 0.037). Soluble (s) IL2Rα exhibited fair diagnostic accuracy (p < 0.001; AUC = 0.717 ± 0.054). In contrast, sIL7Rα and TNFα showed poor discriminatory power despite statistical significance (p < 0.01), with AUC values of 0.675 ± 0.057 and 0.687 ± 0.056, respectively. Results of regression analysis revealed that EDSS, duration of disease, and use of any treatment had no impact on the cytokines. Similarly, no significant correlations were noted between these confounders and cytokines, except a moderate negative correlation (−0.418) between IGF-1 and EDSS. Conclusions: IL18 and IGF-1 have the potential to be used as biomarkers in distinguishing MS from healthy individuals. However, both biomarkers failed to demonstrate the discrimination between various phenotypic patterns of disease, limiting their utility for disease stratification. Future studies with larger, longitudinal cohorts and multi-marker panels are warranted to validate these results and to explore whether combining cytokines with imaging or genetic markers can improve prognostic precision. Full article

Propolis is a chemically complex natural product with recognized antioxidant potential, but its compositional heterogeneity and poor aqueous solubility complicate formulation and interpretation of in vitro release behavior. In this study, a nanostructured lipid carrier (NLC) based on Gelucire^® 44/14 was developed as a physicochemical platform to modulate the accessibility of a selected Chilean ethanolic propolis extract. Propolis extracts from different origins were first screened using complementary antioxidant assays (DPPH, ABTS, ORAC, FRAP), leading to the selection of the Peñaflor extract, which exhibited the highest phenolic content (~41 mg GAE/g) and antioxidant capacity. The selected extract was incorporated into NLCs with encapsulation efficiencies above 90%, a narrow size distribution (~200 nm), and high stability over 90 days. Under simple aqueous conditions, propolis release remained limited (<15% over 6 h), consistent with diffusion- and partition-controlled transport. In simulated gastrointestinal media containing bile components, pronounced pH- and composition-dependent effects were observed. While fed-state intestinal conditions induced extensive morphological remodeling without increasing the analytically accessible fraction (<3% at 4 h), fasted-state intestinal media promoted a higher accessible fraction (~14% within 1 h) without complete carrier disruption, as confirmed by transmission electron microscopy. Preliminary cytocompatibility studies in HepG2 cells showed acceptable viability at 10–40 µg/mL and concentration-dependent effects at higher doses. Overall, this work demonstrates that bile components modulate propolis accessibility through dynamic partitioning and colloidal reorganization rather than simple carrier breakdown, providing a physicochemical framework for future digestion and absorption studies. Full article

Background: Co-delivery of two drugs with diverse physicochemical properties and a specific administration sequence holds great importance in cancer theranostics to overcome drug resistance and reduce side effects. Paclitaxel (PTX) and hydroxycamptothecin (HCPT) have long been used clinically as chemotherapeutic agents for Nasopharyn-geal carcinoma (NPC). However, their clinical application is severely restricted by low water solubility, poor stability, and systemic adverse reactions. Nanoparticle-based drug delivery systems provide a promising platform for combination cancer therapy. Methods: In this study, folic acid-modified and dual drug-loaded self-assembled HCPT/PTX@FA@p-PS-SPIONs were successfully fabricated via the emulsification–solvent evaporation method using amphiphilic phosphorylated polystyrene (p-PS). The characterization, cellular uptake, and in vivo pharmacokinetic profiles of the nanoparticles in NPC models were systematically investigated. Result: HCPT/PTX@FA@p-PS-SPIONs were successfully prepared with p-PS as the copolymer backbone. The nanoparticles exhibited a uniform particle size of 196.9 ± 5.5 nm and a zeta potential of −7.3 ± 0.7 mV. The encapsulation efficiency (EE) was 81.4 ± 2.5% for PTX and 67.6 ± 4.1% for HCPT. The drug loading (DL) efficiency was 18.4 ± 1.5% for PTX and 12.2 ± 1.0% for HCPT. HCPT/PTX@FA@p-PS-SPIONs showed favorable biocompatibility. Sustained and sequential release of the two drugs contributed to an enhanced therapeutic effect. Moreover, under magnetic field (MF) guidance, HCPT/PTX@FA@p-PS-SPIONs exhibited stronger inhibitory effects on NPC cells than single-drug, cocktail, or dual-drug groups, demonstrating the superiority of the combined therapy. Pharmacokinetic studies in rats revealed that the half-lives of PTX and HCPT were 3.9 ± 1.2 h and 4.7 ± 1.1 h, respectively, confirming that HCPT/PTX@FA@p-PS-SPIONs could resist rapid metabolism and clearance in vivo. Conclusions: The long-circulating, folic acid-targeted nanoparticles HCPT/PTX@FA@p-PS-SPIONs show great potential for the targeted therapy of nasopharyngeal carcinoma. Full article

Objectives: Talazoparib (TZL) is a potent PARP inhibitor but suffers from poor aqueous solubility, dissolution-limited absorption, and dose-limiting systemic toxicities, which together restrict its antitumor efficacy in some breast cancer settings. This study aimed to develop a stearic acid-based nanoemulsion (SANE) to improve the delivery of TZL and enhance its antitumor activity and preliminarily explore its impact on DNA damage response-related pathways. Methods: SANE-TZL was prepared using a high-pressure homogenization method, and its physicochemical properties were characterized. MCF-7 and MDA-MB-231 breast cancer cells were used to evaluate cellular uptake, cytotoxicity, and changes in key DNA damage response markers. In vivo therapeutic efficacy and safety were assessed in an MDA-MB-231 xenograft mouse model. Results: SANE-TZL exhibited a uniform particle size of approximately 118 nm with excellent stability. In MCF-7 cells, SANE-TZL significantly enhanced drug internalization, resulting in an 8.4-fold reduction in IC₅₀ compared to free TZL. Consistently, in MDA-MB-231 cells, SANE-TZL also showed markedly increased antiproliferative activity. At the molecular level, SANE-TZL modulated the expression of several DNA damage response-related genes, including BRCA1, RAD51, and SLFN11, in a manner consistent with impaired DNA repair capacity. In vivo, high-dose SANE-TZL achieved a tumor growth inhibition (TGI) rate of 58.55%, which was higher than that of the free TZL group (41.86%) and the blank eSANE group (17.59%). No evident hematological or organ toxicities were observed in the SANE-TZL-treated groups. Conclusions: SANE-TZL markedly improves the delivery efficiency and antitumor activity of TZL in breast cancer models while maintaining a favorable safety profile. By combining a functional stearic acid carrier with TZL, this nanoemulsion formulation represents a safe and potent strategy to enhance PARP inhibitor-based chemotherapy in breast cancer, and it may provide a basis for further mechanistic studies on DNA damage response modulation. Full article

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions—particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients—have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut–eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD. Full article

Background/Objectives: Curcumin (CUR) has shown promising potential as a wound-healing agent for diabetic wounds; however, its efficacy is hindered by poor aqueous solubility and limited skin permeability. To overcome these limitations, CUR was loaded into myrrh oil-based nanoemulsions (NEs). Methods: The NEs were optimized using a three-factor two-level D-optimal mixture design, and characterized for droplet size, polydispersity index, and zeta potential. The optimized NE was subjected to various stability testing and incorporated into a gel base containing insulin (INS) to form CUR-INS nanoemulgel (CUR-INS-NEG). The antibacterial efficacy of CUR-INS-NEG was tested against various bacterial strains, while its wound-healing effects were evaluated in a diabetic rat wound model. Results: The surfactant/co-surfactant concentration had a greater influence on the NE properties than the oil and aqueous phase concentrations. The optimal NE had a droplet size of 155.2 ± 0.8 nm, a polydispersity index of 0.28, and a zeta potential of −31.4 ± 0.8 mV. It demonstrated sustained drug release, with further release control upon incorporation into the gel base. CUR-INS-NEG demonstrated higher in vitro antibacterial efficacy compared with blank NEG, CUR gel, and INS gel. It also showed 2- and 4-fold reduction in the MIC against S. aureus and E. coli, respectively, compared with CUR gel. In a diabetic wound model, CUR-INS-NEG outperformed both CUR gel and INS gel by enhancing anti-inflammatory and antioxidant effects, as well as collagen deposition and endothelial cell proliferation. Conclusions: The CUR-INS-NEG emerges as an effective system for diabetic wound management, delivering complementary anti-inflammatory, antioxidant, and tissue-regenerative effects of myrrh oil, CUR, and INS. Full article