Search Results (232)

This review systematically illustrates the application and research progress of endoscopically delivered hydrogels as a novel strategy in the endoscopic treatment of early-stage gastrointestinal tumors. It focuses on analyzing the unique physicochemical properties, biological functions, and clinical value of hydrogels as submucosal injection materials, and delves into their core roles in achieving sustained mucosal lifting, effective hemostasis, and wound repair during endoscopic submucosal dissection (ESD). Representative hydrogel materials, such as chitosan, hyaluronic acid, and sodium alginate, are driving the evolution of ESD technology from a mere “resection” procedure toward an integrated “lift-resect-repair” therapeutic model, owing to their excellent biocompatibility, injectability, and controllable degradability. Although challenges in clinical translation remain, including long-term safety, precise control of degradation rates, and scalable production, the field is poised for further breakthroughs with the development of smart responsive hydrogels and their deep integration with emerging technologies. Full article

Microneedle systems represent a promising minimally invasive approach for transdermal drug delivery; however, their performance strongly depends on the composition and mechanical properties of the polymer matrix. The aim of this study was to select an optimal polymer composition for the fabrication of dissolving microneedle arrays produced by the mold casting method. The study focused on evaluating mechanical strength, dissolution behavior, and penetration efficiency of different polymer systems. Microneedle matrices were fabricated using polyvinylpyrrolidone (PVP K-30), methylcellulose, sodium alginate, and hyaluronic acid at various concentrations, alone and in combination. No active pharmaceutical ingredient (API) was incorporated; the study was performed using blank polymeric systems intended for subsequent drug loading. The microneedles were manufactured using 3D-printed and silicone molds. Their performance was evaluated by in vitro dissolution testing, pH measurement, penetration studies in gelatin gel and Parafilm M models, and mechanical compression testing. Monopolymer systems demonstrated either rapid dissolution with insufficient mechanical strength or improved strength at the expense of prolonged dissolution time. Combined polymer formulations showed superior structural uniformity and balanced performance. In particular, the system containing 5% PVP K-30 and 10% sodium alginate demonstrated the best overall characteristics, achieving high penetration efficiency (up to 96%), uniform dissolution (78%), and appropriate dissolution time (8.5 ± 0.5 min). Addition of hyaluronic acid further improved structural uniformity and handling properties. The results indicate that composite polymer matrices provide an optimal balance between mechanical stability, penetration ability, and dissolution rate. The formulation consisting of 5% PVP K-30 and 10% sodium alginate was identified as the most promising base for further development of drug-loaded dissolving microneedle systems. Full article

Dry eye disease (DED) is a complex ocular surface disorder characterized by tear film instability, chronic inflammation, and epithelial damage, for which current treatments remain limited. Marine-derived bioactive oligosaccharides have attracted increasing interest due to their diverse pharmacological activities and favorable safety profiles. In this study, we investigated the therapeutic potential of neoagarotetraose (NA4), a marine oligosaccharide derived from red algal agar, in a murine model of DED. DED was induced in eight-week-old female C57BL/6 mice by topical instillation of 0.2% benzalkonium chloride for seven consecutive days. NA4 was administered topically at concentrations of 125, 250, and 500 mg/L. Therapeutic outcomes were evaluated by tear secretion, corneal fluorescein staining, histopathological analysis, immunofluorescence staining for Ki67, F4/80, IL-1β, IL-6, and TNF-α, TUNEL assay for apoptosis, and ELISA for cytokine levels. NA4 treatment significantly improved tear secretion and reduced corneal fluorescein staining scores. Histological analysis revealed that NA4 preserved corneal epithelial thickness and restored conjunctival goblet cell density. Immunofluorescence analysis revealed that NA4 reversed inflammation-associated epithelial hyperproliferation and attenuated macrophage infiltration. Moreover, NA4 markedly suppressed the expression and tissue levels of IL-1β, IL-6, and TNF-α, and attenuated corneal epithelial apoptosis, with the 500 mg/L NA4 group showing no significant difference in efficacy compared to the positive control 0.1% sodium hyaluronate. These findings demonstrate that NA4, a marine-derived oligosaccharide, exerts multi-targeted protective effects against DED by improving tear film stability, preserving ocular surface integrity, suppressing inflammation, and reducing apoptosis. Our study highlights the potential of marine oligosaccharides such as NA4 as promising candidates for ocular surface disease management and supports the further exploration of marine resources for ophthalmic therapeutic applications. Full article

Degenerative joint disease is a major cause of disability, and although glucocorticosteroids and hyaluronic acid are widely used to reduce inflammation and improve joint mobility, the development of effective delivery systems remains a challenge. This study describes injectable sodium hyaluronate (HA)-based hydrogels modified with synthetic polymers, including polyacrylic acid (PA), ammonium acryloyldimethyltaurate/VP copolymer (AX), a polyvinyl acetate–polyvinylpyrrolidone mixture (PVA–PVP), and polyethylene glycol 4000 (PEG), loaded with prednisolone disodium phosphate (PSP). The aim was to investigate molecular interactions between PSP and HA-based polymer networks and to determine how these interactions influence hydrogel structure, viscosity, and drug release. Viscosity was measured using a Brookfield rotational viscometer, while intermolecular interactions were analyzed by ATR–FTIR and DSC. Drug release was evaluated using a paddle-over-disc apparatus and quantified spectrophotometrically. Release kinetics were analyzed using zero-, first-, and second-order models as well as the Higuchi, Korsmeyer–Peppas, and Peppas–Sahlin equations. PSP incorporation affected the dynamic viscosity of all formulations, and excipient type also significantly influenced hydrogel viscosity. ATR–FTIR and DSC analyses indicated hydrogen bond formation between PSP and the macromolecules of HA, PA, AX, and PEG. The PA-containing formulation formed the most extensive polymer network structure and exhibited the highest viscosity. Drug release followed mainly first-order, Higuchi, and Korsmeyer–Peppas models, while the release exponent n (0.58 ± 0.01–0.60 ± 0.01) indicated anomalous transport. These findings provide molecular insight into drug–polymer interactions in HA-based hydrogels and highlight their potential as injectable systems for intra-articular delivery of PSP. Full article

Objective: The purpose of this systematic review is to evaluate the available scientific literature on the effectiveness of combining sodium hypochlorite and cross-linked hyaluronic acid (xHyA) as an adjunct to non-surgical periodontal treatment. Materials and Methods: Five electronic databases were searched. The study was traced using the PRISMA criteria and publications from ProQuest, Google Scholar, Springer Nature, Scopus, and PubMed. The randomized study was examined using the Cochrane Risk of Bias 2 (RoB) tool and two case series studies were reviewed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Results: The systematic review included four studies (two RCT and two case series). Across the included studies, the adjunctive use of sodium hypochlorite/amino acid gel and cross-linked hyaluronic acid (xHyA) following subgingival instrumentation was associated with improvements in clinical periodontal parameters. Probing pocket depth (PPD) reduction ranged from 1.5 to 5.8 mm, clinical attachment level (CAL) gain ranged from 1.5 to 5.3 mm, and bleeding on probing (BOP) reduction ranged from 57.5% to 65.6%. The improvements were generally more pronounced in deeper periodontal pockets. Minor variations in intervention protocols were observed among studies. Conclusions: The adjunctive use of sodium hypochlorite and cross-linked hyaluronic acid in non-surgical periodontal therapy may be associated with improvements in clinical periodontal parameters, including PPD, CAL, and BOP, particularly in deep pockets. However, the available evidence is limited and heterogeneous, with small sample sizes and short follow-up durations. Therefore, these findings should be interpreted with caution, and further well-designed long-term studies are required. Full article

Background: To evaluate the effects of a preservative-free artificial tear formulation containing trehalose, sodium hyaluronate, and N-acetyl-aspartyl-glutamate (NAAGA) on ocular surface parameters and quality of life in patients with primary open-angle glaucoma (POAG) treated with preserved versus preservative-free prostaglandin analogues. Methods: For this prospective, observational clinical study, thirty-eight patients (76 eyes) with POAG receiving stable topical prostaglandin therapy were enrolled and divided into two groups: preserved prostaglandins (Group 1, n = 44) and preservative-free prostaglandins (Group 2, n = 32). All patients received adjunctive preservative-free artificial tears (trehalose, sodium hyaluronate, NAAGA) three times daily for one month. Assessments at baseline (T0) and 1 month (T1) included best-corrected visual acuity (BCVA), intraocular pressure (IOP), contrast sensitivity, Schirmer test, tear break-up time (BUT), Efron grading scale, Ocular Surface Disease Index (OSDI), visual field (VF) indices (Mean Deviation (MD), Pattern Standard Deviation (PSD), Visual Field Index (VFI)), and quality of life (QoL) measured using Visual Analogue Scales (VAS). Results: After 1 month, both groups demonstrated significant improvement in ocular surface parameters. Schirmer test increased by approximately 4–5 mm (p = 0.001 in both groups), and BUT improved by 5 s (p = 0.001 in both groups). OSDI scores significantly decreased (Group 1: –18.5; Group 2: –23; p = 0.001 for both), and Efron grading significantly improved (p = 0.001 in both groups). Artificial tears-related QoL markedly increased in both groups (p = 0.001), while pathology-related QoL remained unchanged. IOP showed a modest but significant reduction in both groups (Group 1 p = 0.011; Group 2 p = 0.003), without intergroup differences. VFI significantly improved in both groups from T0 to T1 (Group 1 p = 0.013; Group 2 p = 0.04). Group 1 also showed an improvement in terms of PSD (p = 0.025). Conclusions: Adjunctive treatment with preservative-free artificial tears containing trehalose, sodium hyaluronate, and NAAGA significantly improved tear film stability VF indexes, ocular surface signs and symptoms, and patient-reported QoL in POAG patients treated with prostaglandins, regardless of preservative status. Routine ocular surface optimization should be considered an integral component of comprehensive glaucoma management. Full article

This study focused on elucidating the effects of chitosan (Ch), hyaluronic acid (HA), and titanium dioxide nanoparticles (nano-TiO₂) on the physicochemical characteristics of a model bacterial membrane (layer) composed of the phospholipid DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt). The membrane was prepared on mica using the Langmuir–Blodgett (LB) technique from an aqueous subphase containing Ch, HA and/or TiO₂. Its surface properties were subsequently characterized by optical profilometry and surface free energy estimation. The nanoscale topography of the DPPG layer provided a biomimetic platform that reflects the organization of bacterial membranes, enabling a precise evaluation of how external agents, such as Ch, HA, and nano-TiO₂, modify the surface’s structural and energetic properties. The results showed that the LB films exhibit mildly heterogeneous topography, which can be attributed to lipid domains with distinct molecular packing densities. Depending on the type of biopolymer employed with TiO₂, distinct topographic architectures of the DPPG monolayers were obtained. Furthermore, the presence of nano-TiO₂ was clearly manifested as a topographic irregularity, while the analysis of hydrophilic–hydrophobic properties revealed a structurally perturbed lipid film. The results provide detailed insight into how these specific molecules (Ch, HA, nano-TiO₂) interact at the molecular level with model bacterial membranes, offering a comprehensive picture of cell–microenvironment interactions. Full article

Hyaluronic acid (HA) is widely used in medical, cosmetic, and nutraceutical applications, yet the systemic fate of orally administered HA, particularly non-animal forms, remains poorly characterised. This study investigates the stability, absorption, metabolism, and biological effects of a novel fungal-derived HA extracted from Tremella fuciformis using a sequential in vitro multi-barrier model simulating human physiological compartments, including gastric, intestinal, hepatic, renal, chondrocyte, and keratinocyte environments. Across the gastrointestinal stages, fungal-derived HA demonstrated high structural stability, maintained molecular weight, and exerted superior antioxidant and anti-inflammatory activity compared with sodium hyaluronate. It efficiently crossed the intestinal barrier without increasing hyaluronidase activity, indicating protection from premature enzymatic degradation. In hepatic cells, fungal-derived HA exhibited reduced intracellular uptake and greater extracellular persistence, suggesting lower first-pass metabolism and suggesting improved persistence under in vitro conditions. At peripheral targets, it increased the cluster of differentiation 44 (CD44) expression and HA internalisation in chondrocytes and keratinocytes, supporting anti-inflammatory and pro-regenerative effects. Renal assessments revealed minimal excretion and no cytotoxicity, supporting potential systemic availability. Overall, these results provide the first integrated in vitro evidence describing the absorption, distribution, metabolism, and excretion process of fungal-derived HA. This supports the conclusion that this form of HA is stable, biocompatible, and bioactive with therapeutic potential for joint and skin health, as suggested by the in vitro models. Full article

The structure collapse and performance degradation caused by traditional air-drying technology often hinder the practical application of bio-based xerogels as absorbent pads. In this study, chitosan (CS) and different types of polyanions (carboxymethyl cellulose (CMC), sodium alginate (SA), hyaluronic acid (HA), pectin (PT) and xanthan gum (XG)) in different proportions were used to prepare an xerogel resistant to atmospheric pressure air drying collapse, and its potential as an absorption pad was systematically evaluated. The results showed that among all the treatments, CS/CMC xerogel at an optimal mass ratio of 1:3 demonstrated superior comprehensive properties. It exhibited minimal shrinkage (p < 0.05) and high porosity, coupled with an exceptional water absorption capacity (140% higher than CS/PT) and hardness (96% higher than CS/SA and CS/HA). FTIR and XRD revealed that strong electrostatic interactions and potential amide bond formation between CS and CMC resulted in a dense yet homogeneous network with low crystallinity. SEM imaging further corroborated a uniform thin-walled porous structure. This stable network contributed to high toughness, of CS/CMC significantly surpassing the brittle CS/XG and CS/PT xerogels (p < 0.05). CS/CMC xerogel is an ideal absorbent material with high absorption, stability, and controllable structure. Full article

Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic inflammation and progressive cartilage degradation. Mesenchymal stem cell (MSC)-based therapies have demonstrated therapeutic potential; however, increasing evidence suggests that their efficacy primarily arises from paracrine factors, highlighting the potential of cell free approaches. In this study, we developed an injectable, thermosensitive composite hydrogel incorporating adipose-derived MSC (AD-MSC) supernatant within a Pluronic F-127 (PF-127)/sodium hyaluronate (HA) matrix. The hydrogel exhibited a solution state at a low temperature and rapidly transitioned into a stable gel at a physiological temperature without chemical crosslinkers. Microstructural analysis revealed a porous, interconnected three-dimensional network favorable for the sustained release of bioactive factors. In a rat model of KOA, intra-articular administration of the AD-MSC supernatant-loaded hydrogel significantly improved joint architecture and locomotor performance, alleviated synovial inflammation, and preserved cartilage integrity. Radiographic and histological assessments demonstrated reduced cartilage degeneration and subchondral bone alterations. Moreover, the treatment markedly decreased intra-articular levels of proinflammatory cytokines (IL-1β and TNF-α) and the cartilage degradation marker CTX-II in a time-dependent manner. These findings indicated that the sustained local delivery of AD-MSC-derived supernatant effectively modulated joint inflammation and attenuated cartilage degeneration, with the hydrogel serving primarily as a delivery vehicle for these bioactive factors. This cell-free injectable biomaterial platform could offer a promising therapeutic strategy for the treatment of knee osteoarthritis. Full article

Background: Artemisia annua L. is a medicinal plant with documented antimicrobial, antioxidant, and anti-inflammatory properties. Although widely studied for internal therapeutic applications, its topical use—especially in hydrogel-based systems—has not been thoroughly investigated. The aim of this study was to develop sodium alginate hydrogels containing Artemisia annua extract, supplemented with hyaluronic acid and dexpanthenol, and to evaluate their physicochemical characteristics as well as their biological activities in vitro and in vivo. Methods: Select bioactive constituents of the Artemisia annua extract were quantified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS). Hydrogels were prepared by cross-linking sodium alginate with a calcium carbonate–glucono-delta-lactone system and were formulated with or without hyaluronic acid and dexpanthenol. Physicochemical evaluations included measurements of moisture content, water-retention capacity, gelation time, and pH. The hydrogel microstructure was examined by scanning electron microscopy (SEM). Antioxidant activity was assessed using three methods: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the ferric reducing antioxidant power (FRAP) assay, and the cupric reducing antioxidant capacity (CUPRAC) assay. Biocompatibility and regenerative effects were analyzed using cell viability assays and an in vitro scratch wound model on human keratinocyte cells. In vivo wound-healing efficacy was examined in rats with full-thickness skin excisions. Results: The extract contained high levels of methylated flavonoids and sesquiterpenes characteristic of Artemisia annua. Hydrogels supplemented with hyaluronic acid and dexpanthenol exhibited improved hydration stability and higher porosity. All formulations demonstrated measurable antioxidant activity, and those containing hyaluronic acid showed the strongest effects. The preparations were biocompatible and enhanced keratinocyte migration in vitro, with the combined hyaluronic acid–dexpanthenol formulation promoting the fastest wound closure. In vivo, Artemisia annua hydrogels accelerated wound healing by two to three days compared with untreated wounds. Conclusions: These results confirm the promise of Artemisia annua hydrogels for topical wound care and highlight the beneficial contributions of hyaluronic acid and dexpanthenol to their structural and therapeutic performance. Full article

Laurus nobilis hydrosol (HyLN), a water-soluble byproduct of essential oil extraction, containing beneficial antioxidants and antimicrobial compounds, was used as a sustainable ingredient in the development of a natural antioxidant-rich hydrogel formulation. Hydrogels were formulated using sodium hyaluronate and xanthan gum, natural ingredients with beneficial effects on the skin, while β-cyclodextrin (βCD) was added to enhance the stability of antioxidants in HyLN. Extensive rheological and textural analyses were employed to optimize the hydrogel formulation for dermal administration, while stability studies assessed the chemical and physical stability of developed formulations. A combination of sodium hyaluronate and xanthan gum provided several HyLN hydrogel formulations with tunable rheological and textural properties, presenting adequate physical and microbiological stability over 6 months of storage. The use of βCD failed to stabilize inherently unstable antioxidants in HyLN hydrogels, yet their residual antioxidant activity remained notable. An in vitro scratch test using a human keratinocyte cell line showed that the developed HyLN gel does not interfere with wound healing. HyLN hydrogels showed a pronounced occlusive effect in vitro, reaching up to 80% of that measured for Vaseline, which helps maintain skin hydration and appearance. Full article

Background/Objectives: Conventional wound care often fails to address the complex pathology of diabetic wounds adequately. Research shows that hyaluronic acid and its derivatives promote tissue regeneration in the later stages of wound healing. We evaluated the efficacy of a novel topical formulation in promoting socket healing following post-extraction in patients with type-2 diabetes mellitus, by combining sodium hyaluronate and six amino acids involved in collagen synthesis. Methods: A single-center, two-arm randomized controlled trial was conducted in adults aged 18 and over with type 2 diabetes requiring extraction of at least one non-impacted tooth. Forty-four participants were randomized to receive either the intervention or no treatment. Primary outcomes included a modified Landry’s healing index and rate of socket closure. Results: Comparative analysis showed significantly improved healing index scores in the intervention group by day 7 and day 14 compared to control, with no improvements in the rate of socket closure. Conclusions: This research provides evidence on the therapeutic efficacy of the gel formulation under study in promoting wound healing of post-extraction sites in diabetic patients undergoing tooth extraction. Further research is needed to compare its efficacy with standard treatments and adjunct therapies. Full article

We herein demonstrate that the thiosemicarbazone (TSC) ligand N′-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) can coordinate with Ga³⁺ to give cationic complex [Ga(L)₂]NO₃ featuring an octahedral Ga(III) center. [Ga(L)₂]NO₃ undergoes metathesis with both Fe²⁺ and Fe³⁺, resulting in the formation of respective Fe²⁺- and Fe³⁺ complexes. [Ga(L)₂]NO₃ is also susceptible to anion exchange with sodium hyaluronate (NaA) to produce the nanoformulation [Ga(L)₂]A with boosted aqueous solubility and cell targeting. [Ga(L)₂]A demonstrated remarkable in vitro cytotoxicity against NCI-H82 and A549 (lung cancer), as well as KYSE-510 and Te-1 (esophageal cancer) cell lines, featuring half maximal inhibitory concentration (IC₅₀) values in the range 0.102–2.616 μmol L⁻¹. This work highlights the potential of using non-toxic and biocompatible Ga³⁺ as the central ion to prepare TSC-based nanomedicines for combating cancer. Full article

Background: Dry eye disease (DED) is characterized by tear film instability and a hyperosmolar ocular surface, which significantly impacts ocular health. Artificial tear solutions (ATSs) have been effective frontline treatments for DED, yet current commercially available products often provide only temporary relief, necessitating frequent daily administration. Significant efforts have been made to develop next-generation ATSs that can provide prolonged protective effects for DED. High-molecular-weight sodium hyaluronate (HA) is more commonly used in multi-dose preservative ATSs due to its longer chain lengths and rheological properties that can provide an enhanced retention time and clinical comfort and effects. The current methods to evaluate ATSs have largely focused on human biocompatibility and rheological testing and often overlook the dynamic nature of cellular phenotypes or the protective mechanisms at a cellular level. Therefore, this study developed novel in vitro mammalian cell assays involving human corneal epithelial cells (HCECs) to comprehensively assess ATSs with HA for biocompatibility and efficacy. Methods: We evaluated cellular viability across varying severities in two distinct DED models: desiccation and hyperosmotic stress. Simultaneously, time-lapse imaging coupled with computational image analyses quantified subtle, yet significant, cellular morphological changes under these stress condition. Results: Our assays revealed that ATSs provide significant, yet varying, protection against mild, medium, and harsh desiccation stress, as well as hyperosmotic conditions. This study also made a key insight that was the observation that DED conditions induce drastic HCEC morphological changes, including significant cellular monolayer breakage, which were effectively mitigated by the ATS products used in this work. Conclusions: The assays presented here provide a robust standard for ATS testing, ultimately guiding the selection of more effective next-generation therapies and aiding in a greater understanding of DED pathogenesis. Full article