Search Results (544)

Magnesium alloys exhibit promising application prospects in medical orthopedic implants. However, their practical applications are limited by rapid corrosion, suboptimal osseointegration, and implant-related infections. Although conventional drug-eluting polymer coatings can provide various biological functions, the uncontrolled drug release often compromises long-term therapeutic efficacy. In this study, a self-healing Mg-poly(ε-caprolactone) (PCL)@OHF coating is designed and prepared on WE43 Mg by spin coating to achieve ultrasound-triggered release of osthole. OHF consists of osthole-loaded hollow mesoporous silica nanoparticles (HMSs) modified with Pluronic F127. Drug release studies show that the nanocapsules respond to ultrasound stimulation, with the cumulative release increasing from 39.94% to 75.93% after 7 days. Furthermore, the coating demonstrates intrinsic self-healing capacity upon thermal treatment at 50 °C. Electrochemical and immersion tests reveal that the composite coating provides good barrier protection for the WE43 Mg alloy, evidenced by a decrease in corrosion current density from 2.04 × 10⁻⁶ to 5.94 × 10⁻⁷ A/cm². In vitro biological assays confirm the antibacterial efficacy against Staphylococcus aureus and Escherichia coli, as well as the ability to promote osteogenic differentiation. The results reveal a surface modification strategy that combines self-healing, anticorrosion, and on-demand drug release, offering a promising approach for advanced orthopedic implants. Full article

Naringenin (NRG), a poorly water-soluble flavonoid with anticancer potential, suffers from limited bioavailability due to low aqueous solubility and poor membrane permeation. In this study, NRG nanocrystals (NRG-NCs) were developed using an optimized antisolvent precipitation–probe sonication method and incorporated into a 20% (w/w) Pluronic^® F127 hydrogel for enhanced delivery. The optimized NRG-NCs exhibited a mean particle size of ~195 ± 5 nm, polydispersity index of ~0.20 ± 0.02, and zeta potential of −24 ± 3 mV. Percentage yield and drug loading capacity were 88.6 ± 2.3% and 78.4 ± 1.8%, respectively. Nanocrystal formation resulted in ~9-fold enhancement in saturation solubility compared to raw NRG. The NRG-NCs gel demonstrated rapid dissolution (~90% release within 120 min) and ~2.5-fold higher ex vivo permeation across the Strat-M^® membrane relative to pure NRG. The hydrogel exhibited suitable physicochemical properties (viscosity ~12,850 cP; pH 6.2 ± 0.1; spreadability 5.8 ± 0.3 cm) and maintained >92% drug content after 30 days of refrigerated storage. Mechanistic studies revealed dose-dependent cytotoxicity, characterized by increased intracellular ROS, mitochondrial membrane depolarization, and elevated caspase-3 activity, confirming ROS-mediated apoptosis. In conclusion, the nanocrystal–hydrogel platform significantly enhances the solubility, permeation, and pro-apoptotic efficacy of NRG, demonstrating its potential for skin cancer treatment. Full article

Inspired by their biocompatibility and thermoreversible gelation—transitioning from room temperature liquids to body temperature gels—Pluronic hydrogels were employed in this study to optimize intracanal penetration and ensure medicament stability. We developed a silver nanoparticle (AgNP)-loaded Pluronic gel (AgNPs-P-gel) as a biocompatible, easily removable intracanal medicament. Following PRILE 2021 guidelines, AgNPs-P-gels (F127/F68) were evaluated for gelation, AgNP release, and antibacterial activity against Enterococcus faecalis and Streptococcus mutans via minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and growth curves. Biofilms in bovine teeth were quantified using CFUs and scanning electron microscope (SEM) imaging. Biocompatibility was tested in L-929 fibroblasts using MTT assays and RT-qPCR for pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). Removal efficacy from bovine canals was microscopically scored. The optimized formulation (20% F127, 7.5% F68) gelled at 34 °C with sustained release over 168 h. AgNPs-P-gel showed strong antibacterial activity (MIC: 25–50 µg/mL). In ex vivo models, 100 µg/mL AgNPs-P-gel (AgNPs-100-P-gel) reduced bacterial counts comparably to calcium hydroxide and chlorhexidine, but with lower cytotoxicity. Although inducing cytokine expression similar to conventional medicaments, AgNPs-P-gel demonstrated significantly superior removability. Thermoreversible AgNPs-P-gel offers sustained antimicrobial action, favorable biocompatibility, and superior removability, potentially improving endodontic disinfection predictability as a calcium hydroxide alternative. Full article

Background and Objectives: Burn wounds are associated with delayed healing, infection, and pathological scarring. Effective repair requires tightly regulated immune and oxidative stress responses, including macrophage polarization. This study evaluated the association of the photosensitizer Rose Bengal, delivered in a hydrogel vehicle, with macrophage polarization and oxidative stress after burn injury. Materials and Methods: Three female red Duroc pigs underwent full-thickness contact burns followed by excision and autografting. Wounds received 20% Pluronic F-127 hydrogel containing 0.1% Rose Bengal sodium, hydrogel alone, or PBS (phosphate-buffered saline) on days 1, 7, and 14 post-burn. Biopsies from days 7 and 120 were analyzed by immunohistochemistry for pan-macrophage marker, CD206 (M2 macrophages), CD3E (T-cell infiltration), and 4-hydroxynonenal (4-HNE; oxidative stress marker). Mean fluorescence intensity was analyzed using two-way ANOVA with Tukey’s post hoc test (mean ± SD, p < 0.05). Results: At day 120, Rose Bengal treatment showed higher pan-macrophage expression (0.80 ± 0.07) compared with PBS (0.62 ± 0.10; p = 0.0034), whereas the difference versus hydrogel (0.68 ± 0.07; p = 0.0628) was not significant. CD206 expression was similarly higher in Rose Bengal-treated wounds (0.77 ± 0.06) compared with PBS (0.62 ± 0.05; p = 0.0277); hydrogel also differed from PBS (p = 0.0287), without a difference between hydrogel and Rose Bengal. For CD3E, a significant main effect of treatment was observed (F(2,12) = 8.346, p = 0.0054), with lower values in Rose Bengal versus PBS at day 120 (p = 0.0360). No differences in 4-HNE were detected. Conclusions: Rose Bengal–hydrogel treatment was associated with increased macrophage presence and enhanced M2 polarization without increased T-cell infiltration. Effects were significant versus PBS but not hydrogel, suggesting Rose Bengal may contribute to a pro-regenerative immune microenvironment without excessive adaptive activation. Full article

As surgery is the first-line paradigm for many solid tumors, precision in preoperative diagnosis and intraoperative imaging is of significant importance. Dual MRI and NIR-II fluorescence imaging could fulfill precision imaging requirements in treating cancers, because of its deep penetration and real-time high spatiotemporal resolution. Thus, the design of dual MRI/NIR-II fluorescence contrast agents is crucial for the diagnosis and surgery of cancers. Herein, we developed optically transparent NaGdF4 matrix-based downshifting nanoparticles (DSNPs) co-doped with Nd³⁺, Yb³⁺, and Er³⁺ as a single nanoplatform for dual NIR-II fluorescence and T1-weighted MRI. Systematic dopant engineering reveals that optimal Nd³⁺ loading enhances cascade Nd → Yb → Er energy transfer and yields intense NIR-II emission at 1334 and 1521 nm upon 808 nm excitation with a relative quantum yield of 1.55, while the presence of Gd³⁺ in the optically transparent matrix imparts strong T1 contrast (4.98 s⁻¹ mM⁻¹). The Pluronic F-127 surface coating confers colloidal stability and biocompatibility. In vitro assays confirm negligible cytotoxicity and efficient cellular uptake. In vivo studies in subcutaneous 4T1 tumor-bearing mice demonstrate robust accumulation, high tumor-to-background contrast in both MRI/NIR-II fluorescence and enable precise NIR-II fluorescence imaging-guided surgery with real-time margin visualization. Therefore, dopant-engineered DSNPs represent a promising dual-modal imaging agent for deep-tissue diagnostic and real-time surgical guidance in precision oncology. Full article

Three new Mn(II) complexes with imidazo[1,2-a]pyridine derivatives were synthesized and structurally characterized in a solid state by single crystal X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analyses. The investigated compounds include [Mn(3-Climpy)₂Cl₂(MeOH)₂] (1), [Mn(3-Brimpy)₂Cl₂(MeOH)₂] (2), and a rare double chloro-bridged coordination polymer [Mn(impy)₂Cl₂]_n (3). Spectroscopic studies were used to assess their potential stability in DMEM (Dulbecco’s Modified Eagle Medium), and encapsulation in Pluronic P-123 micelles improved their solubility in aqueous solution, as well as cellular uptake and selectivity. Biological evaluation revealed negligible cytotoxicity against most cancer and control cell lines, but unexpectedly high activity against pancreatic adenocarcinoma (PANC-1), exceeding that of cisplatin. Complex 2, bearing a bromine substituent in the imidazole ring, showed the strongest effects, correlating with enhanced intracellular accumulation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential disruption. Molecular docking and protein binding assays demonstrated moderate affinity toward human serum albumin (HSA) and transferrin, whereas DNA interaction was weak and non-damaging. These results highlight the structure–activity relationship of Mn(II) imidazo[1,2-a]pyridine complexes and support their potential as targeted redox-active agents against pancreatic cancer, with polymeric encapsulation providing an effective strategy to enhance biological performance. Full article

This work presents the synthesis, characterization, and application of zirconium oxide (ZrO₂)-based catalysts, modified with macro (silica nanospheres, NSP-SiO₂) and mesopore templates (Pluronic 123), impregnated with tungstophosphoric acid (TPA), in the catalytic pyrolysis of tomato agro-industrial residues. The NSP-SiO₂ (SXX) and P123 (PYY) amount mainly influences the ZrO₂SXXPYY-specific surface area (S_BET) and average pore diameter (D_p). ³¹P MAS NMR and FT-IR characterization results show that TPA (H₃PW₁₂O₄₀) was partially transformed into [P₂W₂₁O₇₁]⁶⁻ and [PW₁₁O₃₉]⁷⁻ during the synthesis steps. The acidic properties of ZrO₂SXXPYY samples containing 25 and 50 wt% of TPA (ZrO₂SXXPYYT25 and ZrO₂SXXPYYT50, respectively) are dependent on both the TPA content and the support nature. Bio-oil composition and product selectivity were strongly influenced by the textural and acid-based properties of the catalysts. Notably, non-catalytic pyrolysis favored pathways leading to C2 compounds, with a high content of acetic acid and hydroxyacetone. In contrast, the use of catalysts promoted the formation of higher molecular weight oxygenated compounds (C5–C6), specifically furans, aldehydes, and ketones. Full article

Background/Objectives: The development of stimuli-responsive hydrogels for biomedical uses is an intense field of research. The use of dendritic crosslinkers can enhance the control over the structure and properties of the networks. This work presents a comparative study on the design and evaluation of Pluronic L35 thermogels, incorporating either hydrophobic carbosilane dendrimers (CBS, generations 1 to 3) or hydrophilic dendritic polyglycerols (dPG, 10 k) as crosslinkers. Methods: The thermogels were synthesized via UV-initiated thiol–ene click chemistry. Additionally, they were characterized through swelling studies, mechanical properties, degradation kinetics as well as loading and release studies of the antitumor drug doxorubicin as poorly soluble model cargo. Results: The incorporation of dendritic crosslinkers allowed higher control over the crosslinking process, while the amphiphilic polymer imparted temperature-responsive properties to the resulting networks. Remarkable differences were observed in swelling behavior, mechanical properties and degradation kinetics, depending on the nature of the dendritic crosslinker. Additionally, regarding doxorubicin loading and release in water, CBS hydrogels produced a sustained release over one week, led by network swelling, while dPG hydrogels exhibited a burst release in 4–24 h but were limited by the stronger interaction of DOX with the dPG scaffold. Conclusions: The study provided useful insight for the tailoring of dendritic thermogels for specific biomedical uses such as controlled drug delivery. 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

Nanotechnology has emerged as a promising option in combating the worsening situation with antibiotic resistance. We studied the antimicrobial effectiveness of four types of green synthesized zinc oxide nanoparticles (ZnO-NPs), obtained via Pluronic-assisted co-precipitation by lavender and thyme essential oils and their praseodymium-doped variants. Resazurin Microtiter Assay was applied to a panel of Gram-positive and Gram-negative bacteria from Risk 1 and 2 groups and the ESKAPE group. In relation to the pro-oxidative features of the ZnO-NPs, the production of superoxide dismutase (SOD) and catalase (CAT) in the tested microorganisms was also investigated, as these enzymes are important participants in the antioxidant defense of the bacterial cell and are considered virulence factors. We hypothesized that the sensitivity of microorganisms to the action of ZnO-NPs is related to their innate levels of antioxidant enzyme activity. The results showed that all types of studied ZnO-NPs had an antibacterial effect against the entire panel of tested strains, but with different potencies. The strongest effect was found for Arthrobacter nicotianae, Oerskovia paurometabola, Bacillus subtilis, and Escherichia coli. Less inhibition was observed for bacteria from Risk group 2 maybe due to their better antioxidant protection, especially for Pseudomonas aeruginosa. Praseodymium doping contributed to enhancing the bactericidal effect. A correlation between susceptibility of bacteria to ZnO-NPs and their antioxidant enzyme activity was observed. Full article

Background/Objectives: Hydrogels infused with silver nanoparticles (AgNPs) are widely used for their antibacterial properties, yet their stability, specifically upon contact with solid growth media (agar), remains poorly explored. This study compared two hydrogel matrices, anionic Carbopol 934 and non-ionic Pluronic F127, incorporating AgNPs of three different sizes. The evaluation focused on colloidal stability and antibacterial efficacy against Gram-positive and Gram-negative bacteria. Methods: In this study AgNPs (~20, ~55, and ~65 nm) were synthesised via a wet-chemical method and characterised by UV–visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). AgNPs were incorporated into Carbopol 934 and Pluronic F127 hydrogel matrices. Colloidal stability was monitored over four months of storage and upon contact with tryptic soy agar (TSA). Antibacterial activity was assessed using agar diffusion assays. Results: Showed that both hydrogel systems maintained AgNP stability during storage, comparable to aqueous suspensions. However, upon contact with TSA, aggregation of Carbopol–AgNP hydrogels occurred, whereas Pluronic–AgNP hydrogels remained stable. In antibacterial assays, both hydrogels produced larger zones of inhibition (ZOI) than AgNP suspensions against Gram-negative bacteria (E. coli, P. aeruginosa), with Carbopol–AgNP hydrogels demonstrating superior efficacy in an inverse size-dependent manner. Against Gram-positive bacteria (S. aureus, S. epidermidis), Pluronic–AgNP hydrogels initially showed larger ZOIs due to the polymer’s intrinsic antibacterial activity. However, after correcting for this baseline, Carbopol–AgNP hydrogels exhibited superior net efficacy, with S. epidermidis showing greater susceptibility than S. aureus. Conclusions: While both Carbopol 934 and Pluronic F127 stabilise AgNPs during storage, the matrix type significantly influences behaviour at the biological interface. Carbopol–AgNP hydrogels aggregate upon contact with solid agar yet deliver superior, size-dependent antibacterial activity compared to the stable but less potent Pluronic systems. Full article

Wound healing is frequently compromised by excessive oxidative stress, prolonged inflammation, and inadequate tissue regenerative capacity. To address these challenges, a thermosensitive and injectable composite hydrogel based on Pluronic F127 (F127), phosphatidylcholine (PC), and L-lysine (Lys) was developed for the sustained delivery of sinomenine–gallic acid nanoparticles (SGNPs) and the acceleration of wound repair. The hydrogel undergoes a rapid sol–gel transition at physiological temperatures through physical interactions, enabling excellent injectability and in situ gelation. The optimized composite hydrogel exhibited improved mechanical properties, enhanced structural stability, and a uniform porous microarchitecture. The F127−Lys−PCF127−Lys−PC@SGNPs hydrogel showed superior overall stability and hemocompatibility while enabling the sustained release of SGNPs for up to 24 h. Benefiting from the incorporation of SGNPs, the composite hydrogel displayed enhanced antioxidant activity, effectively scavenging free radicals and alleviating cellular oxidative stress. In vitro experiments demonstrated that the hydrogel promoted keratinocyte migration and proliferation. Furthermore, in a murine full-thickness skin wound model, treatment with F127−Lys−PCF127−Lys−PC@SGNPs significantly accelerated wound closure and facilitated re-epithelialization, angiogenesis, and collagen deposition. Collectively, this multifunctional thermosensitive hydrogel provides a promising platform for advanced wound dressings that integrate sustained delivery, antioxidant protection, and tissue regeneration. Full article

A novel co-encapsulation platform based on curcumin-loaded liposomes (Cur-Lip) incorporated into thermosensitive hydrogels (TSH) was developed to address the physicochemical and biological limitations of topical curcumin (Cur) delivery. Response Surface Methodology (RSM) was used to optimize Pluronic^® F-127, glycerol, and alginate concentrations with respect to gelation time and viscosity. The optimized formulation (22% Pluronic^® F-127, 5% glycerol, and 0.5% alginate) exhibited rapid time sol–gel transition (~86 s), suitable viscosity (~377 mPa·s), excellent model fitting (R² = 0.99) and prediction accuracy. Three formulations (TSH, Cur-TSH, and Cur-Lip-TSH) were subsequently prepared and displayed appropriate thermoresponsive behavior. The Cur-Lip system showed high encapsulation efficiency (~78%). Upon incorporation into the TSH, Cur-Lip-TSH displayed increased viscosity and mechanical strength at physiological temperature. In vitro studies confirmed its cytocompatibility toward human keratinocytes, significant antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, and no irritation potential as assessed by the Hen’s Egg Test on the Chorioallantoic Membrane assay (HET-CAM). Overall, Cur-Lip-TSH represents a safe and robust thermosensitive platform that provides a foundation for future studies on controlled curcumin release and topical performance. Full article

Background: Diabetes mellitus is common and associated with numerous complications including diabetic foot ulcers (DFU), which affect a third of patients and are associated with high morbidity and mortality. There are limited pharmacologic treatment options available with mixed efficacy. We have developed a novel therapeutic targeting inflammation and oxidative stress by conjugating microRNA-146a to cerium oxide nanoparticles to create CNP-miR146a and have found that injectable CNP-miR146a is associated with improved wound healing in a diabetic murine model. We hypothesized that a topical formulation of CNP-miR146a would be associated with equivalent improvements in wound healing. Methods: Release tests of CNP conjugated to fluorescein isothiocyanate were performed to determine the optimal gel base for sustained release. Diabetic (db/db) mice were cutaneously wounded and treated with topical CNP-miR146a, empty gel, injectable CNP-miR146a, or injectable phosphate-buffered saline (PBS). Wound healing over time was compared between groups. Histological samples were collected and analyzed for CD45 and CD31 positivity at multiple timepoints. Results: CNP-miR146a in a topical pluronic lecithin organogel (PLO) base was associated with significantly improved wound healing compared to empty gel or injected PBS and equivalent to injected CNP-miR146a. Treatment with CNP-miR146a was also associated with decreased CD45 positivity and increased CD31 positivity, suggesting decreased inflammation and improved angiogenesis. Conclusions: Topical delivery of CNP-miR46a in a PLO base holds significant promise as a potential therapeutic for DFU and may improve patient compliance due to ease of delivery. Full article

Background/Objectives: Keratitis is an ocular disease caused by microbial infection or by non-infectious damage due to UV light exposure, chemical exposure, or eye injuries. Methods: Moxifloxacin-loaded ufasomes (MOX-UFAs) were optimized using a full factorial design (1².2³) after being prepared by the vortex mixing method. The study evaluated the effects of the oleic acid amount, surface active agent (SAA) amount, and SAA type as independent factors on the entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount released after 6 h (Q6h%). Results: The optimized ufasomes (UFAs) formulation was spherical, with an EE% of 78.37 ± 3.91%, PS of 203.13 ± 20.31 nm, PDI of 0.334 ± 0.016, and ZP of −25.42 ± 1.27 mV. The in vitro release of moxifloxacin (MOX) from the UFAs was maintained for more than 6 h in the range of 40.0–75.0%. The optimum MOX-UFAs formulation was incorporated into an in situ gel (Pluronic F-127/HPMC K4M). The ex vivo studies (corneal permeation and confocal laser scanning microscopy) proved the successful retention of the MOX-UFAs-laden in situ gel. Furthermore, the in vitro and in vivo antimicrobial studies revealed their significant antimicrobial effect against Pseudomonas aeruginosa. In addition, the Draize test proved the tolerability of MOX-UFAs-laden in situ gel in animals. Conclusions: The incorporation of MOX-UFAs into Pluronic F-127/HPMC K4M in situ gel could successfully provide sustained ocular delivery and improve the bioavailability of MOX for the management of keratitis. Full article