Journal of Drug Delivery Science and Technology最新文献

{"title":"Vorinostat polymeric nanoparticle gel: A promising therapy for management of psoriasis","authors":"Tarnjot Kaur ,&nbsp;Nikita Hinge ,&nbsp;Sudeep Pukale ,&nbsp;Mohd Nazam Ansari ,&nbsp;Jyoti Upadhyay","doi":"10.1016/j.jddst.2025.107492","DOIUrl":"10.1016/j.jddst.2025.107492","url":null,"abstract":"<div><div>The present study aimed to develop and evaluate a PLGA-based nanoparticles (PNPs) gel of vorinostat to enhance its therapeutic efficacy in the treatment of psoriasis. Vorinostat-loaded PNPs were prepared using the nanoprecipitation method using minimum amount of solvent and surfactant. The nanoparticles were characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency, while the vorinostat-loaded PNPs gel was evaluated for rheological properties, <em>in vitro</em> drug release, skin permeation, and retention. The optimized PNPs exhibited a mean particle size of 161.70 ± 1.32 nm, PDI of 0.16 ± 0.03, zeta potential of −7.53 ± 0.04 mV, and entrapment efficiency of 89.87 ± 3.28 %. The vorinostat-loaded PNPs gel showed sustained drug release (88.05 ± 0.51 % over 72 h) and a five-fold increase in skin retention (16.82 ± 1.26 μg/cm²) compared to plain vorinostat gel. <em>In vivo</em> evaluation using an imiquimod-induced psoriatic mouse model demonstrated significant improvement in PASI scores, histopathological features, and immunohistochemical markers compared to the marketed formulation and plain vorinostat gel. These findings suggest that vorinostat-loaded PNPs gel offers a promising, scalable, and safer topical strategy for enhanced dermal delivery and effective management of psoriasis.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107492"},"PeriodicalIF":4.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of in vitro bioactivity profile of bee propolis extracts delivered by yeast glucan particles","authors":"Adéla Brejchová ,&nbsp;Eva Králová ,&nbsp;Ondřej Strnad ,&nbsp;Petra Třešňáková ,&nbsp;Giyaullah Habibullah ,&nbsp;Jana Rýparová Kvirencová ,&nbsp;Vojtěch Hrbek ,&nbsp;Jitka Viktorová ,&nbsp;Denisa Lizoňová ,&nbsp;František Štěpánek","doi":"10.1016/j.jddst.2025.107490","DOIUrl":"10.1016/j.jddst.2025.107490","url":null,"abstract":"<div><div>Due to its antibacterial, anticancer and immunomodulatory properties, propolis is widely used in the treatment of various diseases. However, its poor water solubility and bioavailability reduce its effectiveness <em>in vivo</em>. A solution may be found by combining enhanced propolis extraction with loading the extract into a suitable carrier. Here, we investigated glucan particles, obtained from the cell walls of baker's yeast (<em>Saccharomyces cerevisiae</em>), as promising porous carriers capable of increasing the dispersion of propolis and, thereby, its solubility. First, propolis extracts were prepared using a modified sonication method (70 % ethanol at a propolis/ethanol ratio of 1:10); three types of raw propolis differing in source location and year of harvest were used for comparison. Next, lyophilized propolis extracts were loaded into the glucan particles by spray drying and slurry evaporation to ensure the resulting propolis extract content of 10 wt %. ATR-FTIR spectroscopy and SEM confirmed the successful loading into the glucan particles, and UV–VIS spectrophotometry was used to determine encapsulation efficiency. Dissolution tests showed that the loading into glucan particles led to the formation of a supersaturated solution of propolis extract and the enhancement of its dissolution rate. Subsequently, the biological activity of the encapsulated propolis extract was investigated. Overall, the encapsulated propolis extract showed much higher anti-inflammatory, antioxidant and antimicrobial activity than pure propolis. Thus, our results indicate that the combination of propolis extract with glucan particles increases propolis solubility and bioactivity.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107490"},"PeriodicalIF":4.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive investigation of the variables affecting drug release from conventional and adaptive liposomes: Fundamental aspects of cancer therapy","authors":"Anis Askarizadeh ,&nbsp;Maryam Mirhadi ,&nbsp;Mahmoud Reza Jaafari ,&nbsp;Ali Mohammad Tamaddon ,&nbsp;Elaheh Mirhadi","doi":"10.1016/j.jddst.2025.107489","DOIUrl":"10.1016/j.jddst.2025.107489","url":null,"abstract":"<div><div>Several clinically approved liposomal drug formulations have been developed to mitigate side effects associated with severe diseases such as cancer. However, drug release at the targeted site remains insufficient, as demonstrated in the case of Doxil®/Caelyx®. Various strategies have been proposed to utilize both the external and internal tumor environments for the activation of drug release from liposomes. This review article provides a detailed consideration of the numerous factors and variables involved in the optimization of liposome formulations aiming at improving drug release profiles. By screening the arrangement of phospholipids, cholesterol, and polyethylene glycol, the size of liposomes and the aqueous phase of the encapsulated drug can reach controlled drug-release vehicles. Stimuli-responsive liposomes, which respond to external stimuli such as light, heat, and magnetic fields, as well as internal stimuli like redox potential, pH changes, and enzymatic activity, have emerged as a promising approach for achieving controlled drug release. This approach has been discussed thoroughly in this review. Stimuli-responsive liposomes show potential for improving cancer therapies; however, additional investigation is required to connect laboratory discoveries with practical clinical implementation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107489"},"PeriodicalIF":4.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of buspirone hydrochloride nanoparticle temperature-sensitive gel for treating generalized anxiety disorder","authors":"Aiyang Tong ,&nbsp;Hongyu Yang ,&nbsp;Yuou Wang,&nbsp;Ji Li","doi":"10.1016/j.jddst.2025.107487","DOIUrl":"10.1016/j.jddst.2025.107487","url":null,"abstract":"<div><div>Generalized Anxiety Disorder (GAD) is a prevalent anxiety disorder that significantly impairs patients' quality of life. Conventional treatments for GAD often cause adverse reactions, and Buspirone hydrochloride (BUS), a newer anti-anxiety medication, suffers from low bioavailability, thereby limiting its therapeutic effectiveness. Therefore, it is essential to develop a formulation with improved safety and enhanced bioavailability. To address this need, buspirone hydrochloride nanoparticle temperature-sensitive gels (BUS-NPs-GEL) are designed to undergo a temperature-triggered sol-gel transition in the nasal cavity during administration, facilitating sustained release and extended retention of buspirone hydrochloride-chitosan nanoparticles (BUS-NPs). This mechanism facilitates the extended delivery of BUS to the target site, thereby improving therapeutic outcomes. Collectively, the development of buspirone hydrochloride nanoparticle temperature-sensitive gels represents a promising and innovative strategy for the treatment of GAD.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107487"},"PeriodicalIF":4.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Argonaute 2 as an innovative delivery system for siRNA in glioblastoma treatment","authors":"A. Rinaldi ,&nbsp;E. Kluczka ,&nbsp;M. Louis Fathy Nazir ,&nbsp;M. Barbotin ,&nbsp;C. Roy ,&nbsp;L. Basset ,&nbsp;S. Avril ,&nbsp;S. Anthiya ,&nbsp;G. Tosi ,&nbsp;C. Jérôme ,&nbsp;F. Boury ,&nbsp;A. Rousseau ,&nbsp;E. Garcion ,&nbsp;F. Dumas","doi":"10.1016/j.jddst.2025.107459","DOIUrl":"10.1016/j.jddst.2025.107459","url":null,"abstract":"<div><div>RNA interference via small interfering RNA (siRNA) offers promising potential for treating glioblastoma (GB), the most common and aggressive primary brain tumor. While local siRNA delivery could bypass the blood-brain barrier and achieve high drug concentrations, challenges remain in developing effective delivery systems that ensure siRNA stability, efficient cellular uptake, endolysosomal escape, and long-term brain availability. The Argonaute-2 (Ago2) protein, a core component of the RNA interference machinery, naturally binds siRNA and protects it from degradation. Ago2 is also found in biological fluids, such as blood, and in extracellular vesicles, including exosomes and microvesicles, making it a potential natural vector for siRNA delivery.</div><div>This study explores Ago2 as a natural vector for siRNA in nanoparticle-based delivery systems to enhance siRNA transport and gene silencing in GB. Neutral polymeric siRNA/Ago2-loaded nanoparticles (NPs), around 300 nm in size, were formulated with high encapsulation efficiencies (85.1 % for protein and 57.5 % for siRNA). In vitro testing in U87MG GB cells stably expressing luciferase (U87MG Bml1) showed that, in contrast to free siRNA/Ago2 complexes, siRNA/Ago2-loaded NPs effectively reduced luciferase expression compared to scramble siRNA formulations, with no significant cytotoxicity at 48 h. Interestingly, the introduction of exogenous Ago2 into cells unexpectedly upregulated luciferase expression, suggesting that Ago2 may also influence global gene expression beyond its role in siRNA-mediated silencing.</div><div>These findings highlight the potential of siRNA/Ago2-loaded NPs for local siRNA delivery in GB and suggest that Ago2 could play a broader regulatory role in gene expression, in addition to enhancing siRNA activity. Further investigation is needed to explore Ago2's impact on gene regulation and its potential as a therapeutic tool in GB treatment, particularly in combination with biocompatible hydrogels for sustained delivery.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107459"},"PeriodicalIF":4.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrospinning of a bacteriophage-releasing material with antibacterial properties against S. aureus","authors":"Peter Schmieder ,&nbsp;Fanny Salmeron ,&nbsp;Alexia Delnatte ,&nbsp;Lucile Plumet ,&nbsp;Joerg Opitz ,&nbsp;Natalia Beshchasna ,&nbsp;Virginie Molle ,&nbsp;Vincent Cavaillès ,&nbsp;Mikhael Bechelany","doi":"10.1016/j.jddst.2025.107484","DOIUrl":"10.1016/j.jddst.2025.107484","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> causes infections of topical and surgical wounds that may be difficult to treat due to drug-resistance. Much research effort is focused on overcoming this health problem. Bacteriophages could be an option for the treatment of antibiotic-resistant bacterial strains because phages target pathogenic strains with high specificity without affecting the human microbiome. However, the main problem is to incorporate phages in a proper support. In this study, a <em>S. aureus</em>-targeting phage was integrated into polycaprolactone/polyethylene glycol coaxial fibers by electrospinning. The characterization of the physicochemical and mechanical properties of the electrospun materials showed no significant differences in morphology, Young's modulus (∼10 MPa) and tensile strength between the fibers with and without phages. In degradation tests, electrospun fibers with and without phages exhibited the same stability and in aqueous solution, both lost 50 % of their mass (i.e. the PEG component). The lytic activity against <em>S. aureus</em> of the phages incorporated in the electrospun fibers was confirmed <em>in vitro</em> and decreased by 50 % after 30-day storage at 4 °C. Altogether, this proof-of-principle study indicates that phage incorporation into coaxial electrospun fibers represents a promising approach to generate biomaterial with antibacterial properties.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107484"},"PeriodicalIF":4.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-responsive osteopontin-targeted liposomes Co-delivering curcumin and perfluoro-n-pentane for atherosclerosis therapy","authors":"Qingfeng Luo ,&nbsp;Yuyi Deng ,&nbsp;Qiyuan Yang ,&nbsp;Nanxin Zhao ,&nbsp;Can Wang ,&nbsp;Xingsheng Li","doi":"10.1016/j.jddst.2025.107486","DOIUrl":"10.1016/j.jddst.2025.107486","url":null,"abstract":"<div><div>Osteopontin (OPN), highly expressed in foam cells, serves as a hallmark of atherosclerotic plaques and a potential target for site-specific drug delivery. In this study, we developed OPN-targeted liposomes (OPN LIP) co-loaded with curcumin and perfluoro-n-pentane (PFP) to enhance therapeutic efficacy against atherosclerosis. The liposomes exhibited uniform particle size, colloidal stability, favorable biocompatibility, and minimal cytotoxicity. In vitro experiments demonstrated efficient and time-dependent cellular uptake by ox-LDL–stimulated RAW264.7 foam cells. Upon exposure to low-intensity focused ultrasound (LIFU), the nanocarriers underwent acoustic cavitation-induced rupture, leading to rapid curcumin release and significant induction of apoptosis. OPN LIP treatment notably reduced IL-1α and TNF-α levels and aggravated apoptosis in foam cells. Transcriptomic analysis revealed modulation of inflammatory and apoptotic pathways, including TLR, NF-κB, and Mapk3 signaling. These findings highlight the potential of OPN LIP as an ultrasound-responsive, targeted nanoplatform capable of suppressing inflammation and foam cell viability, providing a promising approach for the treatment of atherosclerosis through combined physical and pharmacological strategies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107486"},"PeriodicalIF":4.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal delivery of levocetirizine via transethosomal thermosensitive in situ gel: A promising strategy for enhanced nasal absorption and antihistamine action in allergic rhinitis","authors":"Asmaa Mohamed ,&nbsp;Mohamed El-Nabarawi ,&nbsp;Mahmoud H. Teaima ,&nbsp;Khaled M. Abdel-Haleem ,&nbsp;Ghada M. Ragab ,&nbsp;Hagar Belal Abo-Zalam ,&nbsp;Sammar Fathy Elhabal","doi":"10.1016/j.jddst.2025.107452","DOIUrl":"10.1016/j.jddst.2025.107452","url":null,"abstract":"<div><div>Allergic rhinitis has shown a rising prevalence throughout the years, necessitating the implementation of more effective and safe treatment strategies. Levocetirizine (LVC) is an antihistamine of the second generation used for Allergic Rhinitis, Allergic Conjunctivitis, atopic and contact dermatitis, eczema, and urticaria. This study proposed a transethosomal thermosensitive in-situ gel as an intranasal delivery system experimentally for the first time to treat AR in animal models. LVC-loaded transethosomes (LVC-TEs) were prepared using the thin film hydration method. The zeta potential, particle size, polydispersity index, and entrapment efficiency (EE %) were then evaluated. Additionally, TEM and FTIR investigations were performed on the optimized LVC-TE formulation (TE1). The optimized formula integrates into a thermosensitive in-situ gel based on poloxamer 407 and 188, and hydroxypropyl methylcellulose as a mucoadhesive polymer (TE1-ISG). The evaluation of TE1-ISG involved assessing various parameters, and ex-vivo permeation. TE1 displayed smooth spherical nanoparticles with the highest EE% (92.58 ± 1.21), optimum particle size (130.64 ± 2.10 nm), polydispersity index (0.46 ± 0.04), and zeta potential (19.52 ± 0.52 mV). The release profile of TE1 displayed an initial burst followed by sustained release within 24 h. AR was experimentally induced in 24 rats through ovalbumin sensitization followed by nasal challenges. Serum levels of IgE, histamine, PAF, IL-1β, and IL-5 were measured using ELISA, along with PAF and LTB4 levels in the nasal mucosa. The expression of PGD2 and CCL24 mRNA was analyzed via qRT-PCR. Histopathological and immunohistochemical evaluations were performed to assess TGF-β and FOXO1 expression. This study demonstrates that the developed intranasal TE1-ISG provides an effective delivery platform, showing positive pharmacodynamics effects in treating OVA-induced rhinitis in rats, and represents a novel and promising strategy for AR treatment.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107452"},"PeriodicalIF":4.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroitin Sulphate-based hydrogels loaded with folic acid-functionalized nanoparticles to target colorectal cancer","authors":"Mudassir Abbasi ,&nbsp;Muhammad Sohail ,&nbsp;Syed Ahmed Shah ,&nbsp;Aya Hamid Mohammad Qalawlus ,&nbsp;Syeda Ayesha Farhana","doi":"10.1016/j.jddst.2025.107479","DOIUrl":"10.1016/j.jddst.2025.107479","url":null,"abstract":"<div><div>Colorectal cancer (CRC) patients continue to be a major cause of cancer-associated morbidity and mortality worldwide. Traditional chemotherapies are least effective due to low bioavailability of drugs at tumor locations, off-target systemic toxicity, and poor oral delivery of hydrophobic drugs. This research describes the first smart nanoparticles-loaded hydrogel system (SNHS) capable of targeted, sustained oral delivery of chemotherapeutics. The system combines folic acid-conjugated nanoparticles for targeted delivery to tumors. Along with pH-sensitive polymeric hydrogels capable of controlled release in the gastrointestinal tract. Comprehensive physicochemical analysis, such as X-ray diffraction, FTIR, SEM, thermal analysis, and dynamic light scattering, assured nanoparticles' stability and ligand conjugation. <em>In-vitro</em> studies proved effective drug loading, entrapment, and sustained release profile up to 70 h in simulated gastric and intestinal fluids. Cellular uptake and cytotoxicity tests on folate receptor-positive (HT-29, HeLa) and FR-negative (A-549) cell lines support receptor-mediated nanoparticle internalization and selective toxicity. The MTT assay on non-cancerous CCD841 cells showed the safety of the developed formulations for non-cancerous healthy cells. The in vivo assessment in the Ht-29 xenograft model of colorectal cancer identified significant inhibition of tumor growth and enhanced survival, tracked by IVIS imaging. The synergistic benefits of targeted nanoparticle delivery and hydrogel-mediated sustained release highlight the potential of SNHS as a viable oral therapeutic platform for CRC. This strategy overcomes major limitations of existing chemotherapy by increasing drug bioavailability, specificity, and patient compliance.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107479"},"PeriodicalIF":4.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sacran-based semi-IPN hydrogel with prolonged drug release from curcumin/chitosan nanoparticle and broad bioactivity","authors":"Chengqun Yu ,&nbsp;Abid Naeem ,&nbsp;Maiko Kaneko Okajima ,&nbsp;Tatsuo Kaneko","doi":"10.1016/j.jddst.2025.107485","DOIUrl":"10.1016/j.jddst.2025.107485","url":null,"abstract":"<div><div>Chronic inflammatory diseases and oxidative stress-related conditions remain challenging to manage due to the poor bioavailability, rapid degradation, and systemic toxicity associated with conventional therapies. Curcumin, a natural polyphenol with potent antioxidant and anti-inflammatory properties, holds therapeutic promise but is limited by poor solubility and instability under physiological conditions. Here, we developed a chemically and physically integrated, semi-interpenetrating network (semi-IPN) hydrogel platform for localized and sustained curcumin oral delivery. The hydrogel is composed of poly (2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS), hyaluronic acid (HA), and the supergiant glycosaminoglycanoid, sacran, forming a highly anionic, viscoelastic, highly hydrated and mechanically robust polyelectrolyte network. Curcumin was pre-encapsulated within chitosan/tripolyphosphate nanoparticles (Cur-CSNPs), which were physically entrapped in the hydrogel to confer hierarchical control over drug diffusion. The composite hydrogel exhibited primarily pH-independent, sustained curcumin release, with enhanced swelling capacity and structural integrity attributed to the synergistic interplay of its macromolecular components. <em>In vitro</em> studies demonstrated potent and sustained antioxidant and antibacterial activities against <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>, along with high cytocompatibility in RAW 264.7 macrophages. This macromolecularly engineered, biofunctional hydrogel presents a promising delivery platform for plant-derived bioactives, combining network design with hierarchical drug encapsulation to address key challenges in inflammation-targeted therapeutics.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107485"},"PeriodicalIF":4.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}