RESUMEN

In this study, a novel fluorescence nanoprobe based on Materials of Institute Lavoisier (MIL-101) metal-organic frameworks embedding into the agarose hydrogel is fabricated using a hydrothermal technique. It uses for sensitive quantification of deferiprone in exhaled breath condensate (EBC) samples. The morphology and characterization of MIL-101/agarose nanocomposite hydrogel is studied by transmission electron microscopy, dynamic light scattering instrument, powder X-ray diffraction analysis, and Fourier transform infrared spectroscopy. The probe shows a reasonable fluorescence intensity quenching in the presence of deferiprone due to the interactions between iron centers in MIL-101 (Fe) and deferiprone, which likely form non-fluorescent complexes. The proposed nanoprobe demonstrates a linear calibration curve from 0.005 to 1.5 µg mL- 1 with a detection limit of 0.003 µg mL- 1. The intra- and inter-day precision of the reported method are 0.3% and 0.4% (n = 5, deferiprone concentration = 1.0 µg mL- 1), respectively. This method demonstrates high sensitivity and specificity towards deferiprone in the EBC samples and also presents a sensing platform with simplicity, convenience, fast implementation, and cost-effective in medical monitoring.

RESUMEN

The treatment of infected wounds relies on antibiotics; however, increasing drug resistance has made therapeutic processes more difficult. Activating self-innate immune abilities may provide a promising alternative to treat wounds with bacterial infections. In this work, we constructed an immunogenic injectable hydrogel crosslinked by the Schiff base reaction of carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA) and encapsulated with stimulator of interferon genes (STING) agonist c-di-GMP loaded ZIF-8 nanoparticles (c-di-GMP@ZIF-8). Nanocubic ZIF-8 was screened as the most efficient intracellular drug delivery vector from five differently-shaped morphologies. The NOCC/AHA hydrogel released c-di-GMP@ZIF-8 more quickly (43 %) in acidic environment (pH = 5.5) of infected wounds compared with 34 % in non-infected wound environment (pH = 7.4) at 96 h due to pH-responsive degradation performance. The released c-di-GMP@ZIF-8 was found to activate the STING signaling of macrophages and enhance the secretion of IFN-ß, CCL2, and CXCL12 5.8-7.6 times compared with phosphate buffer saline control, which effectively inhibited S. aureus growth and promoted fibroblast migration. In rat models with infected wounds, the c-di-GMP@ZIF-8 nanocomposite hydrogels improved infected wound healing by promoting granulation tissue regeneration, alleviating S. aureus-induced inflammation, and improving angiogenesis. Altogether, this study demonstrated a feasible strategy using STING-targeted and pH-responsive hydrogels for infected wound management.

RESUMEN

Current skin sensors or wound dressings fall short in addressing the complexities and challenges encountered in real-world scenarios, lacking adequate capability to facilitate wound repair. The advancement of methodologies enabling early diagnosis, real-time monitoring, and active regulation of drug delivery for timely comprehensive treatment holds paramount significance for complex chronic wounds. In this study, a nanocomposite hydrogel is devised for real-time monitoring of wound condition and comprehensive treatment. Tannins and siRNA containing matrix metalloproteinase-9 gene siRNA interference are self-assembled to construct a degradable nanogel and modified with bovine serum albumin. The nanogel and pH indicator are encapsulated within a dual-crosslinking hydrogel synthesized with norbornene dianhydride-modified paramylon. The hydrogel exhibited excellent shape adaptability due to borate bonding, and the click polymerization reaction led to rapid in situ curing of the hydrogel. The system not only monitors pH, temperature, wound exudate alterations, and peristalsis during wound healing but also exhibits hemostatic, antimicrobial, anti-inflammatory, and antioxidant properties, modulates macrophage polarization, and facilitates vascular tissue regeneration. This therapeutic approach, which integrates the monitoring of pathological parameters with comprehensive treatment, is anticipated to address the clinical issues and challenges associated with chronic diabetic wounds and infected wounds, offering broad prospects for application.

RESUMEN

Aiming at dealing with organic and inorganic pollutants dissolved in aquatic environments, we introduce self-assembled fluorescent nanocomposite hydrogel based on a binary polysaccharide network (xanthan gum/chitosan) embedding nitrogen-doped carbon quantum dots not only as a hybrid solid optical sensor for detecting Cr(VI) ions but also to remove anionically charged contaminants Cr(VI) and methyl orange (MO) by acting as an adsorbent. This fluorescent nanocomposite achieved a detection limit of 0.29 µM when used to detect Cr(VI) and demonstrated a fluorescence quantum yield of 59.7 %. Several factors contributed to the effectiveness of the adsorption of Cr(VI) and MO in batch studies, including the solution pH, dosage of the adsorbent, temperature, initial contamination level, and contact time. Experimental results showed 456 mg/g maximum adsorption capacity at pH 4 for MO compared to 291 mg/g at pH 2 for Cr(VI) at 25 °C. In addition to conforming to Langmuir's model, Cr(VI) and MO's adsorption kinetics closely matched pseudo-second-order. Using thermodynamic parameters, the results indicate that Cr(VI) and MO adsorb spontaneously and exothermically. Recycling spent adsorbent for Cr(VI) and MO using NaOH at 0.1 M was possible; the respective adsorption efficiency remained at approximately 82.2 % and 83 % after the fifth regeneration cycle.

RESUMEN

This study reports a pH/magnetic dual-responsive hemicellulose-based nanocomposite hydrogel with nearly 100 % carbohydrate polymer-based and biodegradable polymer compositions for drug delivery. We synthesized pure Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) using a co-precipitation method, then engineering xylan hemicellulose (XH), acrylic acid, poly(ethylene glycol) diacrylate, and Fe3O4 to synthesize the pH/magnetic dual-responsive hydrogel (Fe3O4@XH-Gel), through graft polymerization on XH with in-situ doping Fe3O4 MNPs initiated by the ammonium persulfate/tetramethylethylenediamine redox system. Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectrometer (SEM-EDS), high-resolution transmission electron microscopy (HRTEM), Brunauer-Emmett-Teller (BET), swelling gravimetric analysis, vibrating sample magnetometer (VSM) were employed to analyze the hydrogel's chemical structures, morphologies, pH-responsive behaviors, and magnetic responsiveness characteristics, mechanical and rheological properties, as well as cytotoxicity and biodegradability. The results indicate that the Fe3O4@XH-Gel exhibited excellent dual responsiveness to pH and magnetism. Furthermore, an emphasis was placed on the in-depth analysis of the pH response mechanism. Finally, we utilized this cutting-edge hydrogel to investigate the controlled-release behavior of two model drugs, Acetylsalicylic acid and Theophylline. The hydrogel demonstrated exceptional controlled release attributes, positioning it as a potential carrier for targeted drug delivery, particularly to the gastrointestinal conditions.

Asunto(s)

Hidrogeles , Nanocompuestos , Polisacáridos , Xilanos , Hidrogeles/química , Hidrogeles/síntesis química , Xilanos/química , Concentración de Iones de Hidrógeno , Polisacáridos/química , Nanocompuestos/química , Liberación de Fármacos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Teofilina/química , Teofilina/administración & dosificación , Humanos

RESUMEN

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

Asunto(s)

Antibacterianos , Quitina , Sistemas de Liberación de Medicamentos , Hidrogeles , Nanopartículas , Impresión Tridimensional , Hidrogeles/química , Hidrogeles/farmacología , Quitina/química , Quitina/farmacología , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas/química , Animales , Periodontitis/tratamiento farmacológico , Periodontitis/terapia , Periodontitis/microbiología , Periodontitis/patología , Simvastatina/farmacología , Simvastatina/química , Simvastatina/administración & dosificación , Células Madre Mesenquimatosas/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Porphyromonas gingivalis/efectos de los fármacos

RESUMEN

The complexity and compensatory evolution of tumors weaken the effectiveness of single antitumor therapies. Therefore, multimodal combination therapies hold great promise in defeating tumors. Herein, we constructed a multi-level regulatory co-delivery system based on chemotherapy, phototherapy, and immunotherapy. Briefly, curcumin (Cur) was prepared as nanoparticles and coated with polydopamine (PDA) to form PCur-NPs, which along with an immune checkpoint inhibitor (indoximod, IND) were then loaded into a thermosensitive Pluronic F127 (F127) hydrogel to form a multifunctional nanocomposite hydrogel (PCur/IND@Gel). The in situ-formed hydrogel exhibited excellent photothermal conversion efficiency and sustained drug release behavior both in vitro and in vivo. In addition, PCur-NPs showed enhanced cellular uptake and cytotoxicity under NIR laser irradiation and induced potent immunogenic cell death (ICD). After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8+ and CD4+ antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.

Asunto(s)

Neoplasias de la Mama , Curcumina , Hidrogeles , Inmunoterapia , Indoles , Nanopartículas , Polímeros , Indoles/química , Indoles/farmacología , Curcumina/química , Curcumina/farmacología , Polímeros/química , Polímeros/farmacología , Animales , Nanopartículas/química , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Femenino , Inmunoterapia/métodos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Fototerapia , Terapia Combinada , Terapia Fototérmica , Tamaño de la Partícula , Poloxámero/química , Ensayos de Selección de Medicamentos Antitumorales , Supervivencia Celular/efectos de los fármacos , Propiedades de Superficie , Línea Celular Tumoral , Humanos

RESUMEN

This study developed a nanocomposite hydrogel, CAM4-MMT, for efficiently removing basic fuchsin dye from water. The hydrogel was prepared by grafting a copolymer of acrylic acid (AA) and acrylamide (AM) onto carboxymethyl konjac glucomannan (CMKGM), and doped with montmorillonite (MMT), exhibited excellent thermal stability, a porous inner structure, large specific surface area (1.407 m2/g), and high swelling capacity (107.3 g/g). The hydrogel achieved a maximum adsorption capacity of 694.1 mg/g and a removal rate of 99.5 %. The Langmuir isotherm and pseudo-second-order kinetic model best described the adsorption process. Regeneration and reuse tests confirmed that the hydrogel has excellent recyclability. In conclusion, the CAM4-MMT composite hydrogel efficiently removed basic fuchsin from water solutions, offering a new scheme for eliminating basic fuchsin using natural polysaccharides with promising applications.

Asunto(s)

Acrilamida , Acrilatos , Bentonita , Hidrogeles , Mananos , Mananos/química , Acrilamida/química , Bentonita/química , Hidrogeles/química , Acrilatos/química , Adsorción , Cinética , Colorantes de Rosanilina/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos , Colorantes/química , Concentración de Iones de Hidrógeno

RESUMEN

Red fluorescent hydrogels possessing injectable and self-healing properties have widespread potential in biomedical field. It is still a challenge to achieve a biomacromolecules based dynamic hydrogels simultaneously combining with excellent red fluorescence, good mechanical properties, and biocompatibility. Here we first explore hydrophilic inclusion complex of (R-CDs@α-CD) derived from hydrophobic red fluorescent carbon dots (R-CDs) and α-cyclodextrin (α-CD), and then achieved a red fluorescent and dynamic polysaccharide R-CDs@α-CD/CEC-l-OSA hydrogel. The nanocomposite hydrogel can be fabricated through controlled doping of red fluorescent R-CDs@α-CD into dynamic polymer networks, taking reversibly crosslinked N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) as an example. The versatile red fluorescent hydrogel simultaneously combines the features of injection, biocompatibility, and augmented mechanical properties and self-healing behavior, especially in rapid self-recovery even after integration. The R-CDs@α-CD uniformly dispersed into dynamic hydrogel played the role of killing two birds with one stone, that is, endowing red emission of a hydrophilic fluorescent substance, and improving mechanical and self-healing properties as a dynamic nano-crosslinker, via forming hydrogen bonds as reversible crosslinkings. The novel red fluorescent and dynamic hydrogel based on polysaccharides is promising for using as biomaterials in biomedical field.

Asunto(s)

Alginatos , Carbono , Quitosano , Hidrogeles , Nanocompuestos , Puntos Cuánticos , Alginatos/química , Quitosano/química , Carbono/química , Nanocompuestos/química , Hidrogeles/química , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Colorantes Fluorescentes/química , alfa-Ciclodextrinas/química , Materiales Biocompatibles/química , Animales , Interacciones Hidrofóbicas e Hidrofílicas

RESUMEN

In this study, a functional nanostructured lipid carriers (NLCs)-based hydrogel was developed to repair the damaged epidermal skin barrier. NLCs were prepared via a high-energy approach, using argan oil and beeswax as liquid and solid lipids, respectively, and were loaded with ceramides and cholesterol at a physiologically relevant ratio, acting as structural and functional compounds. Employing a series of surfactants and optimizing the preparation conditions, NLCs of 215.5 ± 0.9 nm in size and a negative zeta potential of -42.7 ± 0.9 were obtained, showing acceptable physical and microbial stability. Solid state characterization by differential scanning calorimetry and X-ray powder diffraction revealed the formation of imperfect crystal NLC-type. The optimized NLC dispersion was loaded into the gel based on sodium hyaluronate and xanthan gum. The gels obtained presented a shear thinning and thixotropic behavior, which is suitable for dermal application. Incorporating NLCs enhanced the rheological, viscoelastic, and textural properties of the gel formed while retaining the suitable spreadability required for comfortable application and patient compliance. The NLC-loaded gel presented a noticeable occlusion effect in vitro. It provided 2.8-fold higher skin hydration levels on the ex vivo porcine ear model than the NLC-free gel, showing a potential to repair the damaged epidermal barrier and nourish the skin actively.

RESUMEN

Background: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue. Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining. Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin. Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.

Asunto(s)

Alginatos , Antiinflamatorios , Pulpa Dental , Hidrogeles , Nanocompuestos , Pulpa Dental/citología , Pulpa Dental/efectos de los fármacos , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Nanocompuestos/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Alginatos/química , Alginatos/farmacología , Pulpitis/terapia , Células Madre/efectos de los fármacos , Células Madre/citología , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Silicatos/química , Silicatos/farmacología , Ratas , Diferenciación Celular/efectos de los fármacos , Compuestos de Calcio/química , Compuestos de Calcio/farmacología , Células Cultivadas , Compuestos de Aluminio/química , Compuestos de Aluminio/farmacología , Arginina/química , Arginina/farmacología , Ratas Sprague-Dawley , Combinación de Medicamentos , Masculino , Óxidos/química , Óxidos/farmacología

RESUMEN

Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual-loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high-mobility group box /receptor for advanced glycation end product/NF-κB (HMGB1/RAGE/NF-κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF-ß)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel-based therapeutic delivery strategies for clinical scarless wound therapy.

RESUMEN

BACKGROUND: Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated. RESULTS: This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors. CONCLUSIONS: These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.

Asunto(s)

Carcinoma Hepatocelular , Hidrogeles , Neoplasias Hepáticas , Nanocompuestos , Ablación por Radiofrecuencia , Sumoilación , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Animales , Hidrogeles/química , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Humanos , Ratones , Ablación por Radiofrecuencia/métodos , Sumoilación/efectos de los fármacos , Línea Celular Tumoral , Masculino

RESUMEN

The healing of critical-sized bone defects is a major challenge in the field of bone tissue engineering. Gelatin-related hydrogels have emerged as a potential solution due to their desirable properties. However, their limited osteogenic, mechanical, and reactive oxygen species (ROS)-scavenging capabilities have hindered their clinical application. To overcome this issue, we developed a biofunctional gelatin-Mxene nanocomposite hydrogel. Firstly, we prepared two-dimensional (2D) Ti3C2 MXene nanosheets using a layer delamination method. Secondly, these nanosheets were incorporated into a transglutaminase (TG) enzyme-containing gallic acid-imbedded gelatin (GGA) pre-gel solution to create an injectable GGA-MXene (GM) nanocomposite hydrogel. The GM hydrogels exhibited superior compressive strength (44-75.6 kPa) and modulus (24-44.5 kPa) compared to the GGA hydrogels. Additionally, the GM hydrogel demonstrated the ability to scavenge reactive oxygen species (OH- and DPPH radicals), protecting MC3T3-E1 cells from oxidative stress. GM hydrogels were non-toxic to MC3T3-E1 cells, increased alkaline phosphatase secretion, calcium nodule formation, and upregulated osteogenic gene expressions (ALP, OCN, and RUNX2). The GM400 hydrogel was implanted in critical-sized calvarial defects in rats. Remarkably, it exhibited significant potential for promoting new bone formation. These findings indicated that GM hydrogel could be a viable candidate for future clinical applications in the treatment of critical-sized bone defects.

Asunto(s)

Gelatina , Hidrogeles , Nanocompuestos , Osteogénesis , Especies Reactivas de Oxígeno , Cráneo , Hidrogeles/química , Hidrogeles/farmacología , Animales , Gelatina/química , Nanocompuestos/química , Osteogénesis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Cráneo/efectos de los fármacos , Cráneo/patología , Ratones , Ratas , Regeneración Ósea/efectos de los fármacos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Titanio/química , Línea Celular , Ingeniería de Tejidos/métodos

RESUMEN

Hydrogel microneedle patches have emerged as promising platforms for painless, minimally invasive, safe, and portable transdermal drug administration. However, the conventional mold-based fabrication processes and inherent single-functionality of such microneedles present significant hurdles to broader implementation. Herein, we have developed a novel approach utilizing a precursor solution of robust nanocomposite hydrogels to formulate photo-printable inks suitable for the direct 3D printing of high-precision, triple-responsive hydrogel microneedle patches through digital light processing (DLP) technology. The ink formulation comprises four functionally diverse monomers including 2-(dimethylamino)ethyl methacrylate, N-isopropylacrylamide, acrylic acid, and acrylamide, which were crosslinked by aluminum hydroxide nanoparticles (AH NPs) acting as both reinforcing agents and crosslinking centers. This results in the formation of a nanocomposite hydrogel characterized by exceptional mechanical strength, an essential attribute for the 3D printing of hydrogel microneeedle patches. Furthermore, this innovative 3D printing strategy facilitates facile customization of microneedle geometry and patch dimensions. As a proof-of-concept, we employed the fabricated hydrogel microneedles for transdermal delivery of bovine serum albumin (BSA). Importantly, these hydrogel microneedles displayed no cytotoxic effects and exhibited triple sensitivity to pH, temperature and glucose levels, thereby enabling more precise on-demand drug delivery. This study provides a universal method for the rapid fabrication of hydrogel microneedles with smart responsiveness for transdermal drug delivery applications.

Asunto(s)

Sistemas de Liberación de Medicamentos , Hidrogeles , Nanocompuestos , Agujas , Impresión Tridimensional , Albúmina Sérica Bovina , Hidrogeles/química , Nanocompuestos/química , Animales , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/administración & dosificación , Administración Cutánea , Bovinos , Tamaño de la Partícula , Humanos , Concentración de Iones de Hidrógeno , Propiedades de Superficie , Temperatura

RESUMEN

BACKGROUND: Due to their excellent stability, low toxicity, flexible modification and adjustable functionality, carbon dots (CDs) have a promising application prospect in the field of chromatographic stationary phases. Hydrogels are new functional polymer materials with three-dimensional network structure that have excellent hydrophilicity, high porosity and unique mechanical properties, which are also good candidate materials for liquid chromatography. Nevertheless, a review of the literature reveals that CDs based nanocomposite hydrogels have not yet been reported as HPLC stationary phases. RESULTS: In this work, amphiphilic CDs with multiple functional groups and polyacrylic acid hydrogel were grafted to the surface of silica gel by an in-situ polymerization method, and a CDs/polyacrylic acid nanocomposite hydrogel stationary phase (CDs/hydrogel@SiO2) was prepared. CDs act as the macroscopic cross-linking agents to form a cross-linked network with polyacrylic acid chains through physical cross-linking by hydrogen bonding and chemical cross-linking by amidation and esterification reactions, which not only improve the swelling property of the hydrogel but also increase its stability. Additionally, the introduction of CDs with multifunctional groups modulates the hydrophilic-hydrophobic balance of the hydrogel that also imparts good hydrophobicity to the composite hydrogel. Through the study of retention mechanism and influencing factors, it is certificate that the CDs/hydrogel@SiO2 has mixed-mode chromatographic performance. Furthermore, the CDs/hydrogel@SiO2 column shows great potential for the determination of organic contaminants in environmental water samples. SIGNIFICANCE: This work confirms the potential application of CDs/hydrogel composite for the separation of various samples and provides the possibility of developing CDs based nanocomposite hydrogel in the field of liquid chromatography. Introducing CDs into hydrogel can open up a new way for nanocomposite hydrogels to be used in HPLC, which expands the advance of hydrogel and CDs in separation field.

RESUMEN

Zinc oxide nanostructures (ZnO NS) were fabricated in situ within a ternary hydrogel system composed of carboxymethyl cellulose-agarose-polyvinylpyrrolidone (CAP@ZnO TNCHs) by a one-pot method employing moist-heat solution casting. The percentages of CMC and ZnO NS were varied in the CAP hydrogel films and then they were investigated by different techniques, such as ATR/FTIR, TGA, XRD, XPS, and FE-SEM analysis. Furthermore, the mechanical properties, hydrophilicity, swelling, porosity, and antibacterial activity of the CAP@ZnO TNCHs were studied. In-vitro biocompatibility assays were performed with skin fibroblast (CCD-986sk) cells. In-vitro culture of CCD-986sk fibroblasts showed that the ZnO NS facilitated cell adhesion and proliferation. Furthermore, the application of CAP@ZnO TNCHs enhanced cellular interactions and physico-chemical, antibacterial bacterial, and biological performance relative to unmodified CAP hydrogels. Also, an in vivo wound healing study verified that the CAP@ZnO TNCHs promoted wound healing significantly within 18 days, an effect superior to that of unmodified CAP hydrogels. Hence, these newly developed cellulose-based ZnO TNCHs are promising materials for wound healing applications.

Asunto(s)

Nanoestructuras , Óxido de Zinc , Hidrogeles/farmacología , Hidrogeles/química , Óxido de Zinc/farmacología , Óxido de Zinc/química , Carboximetilcelulosa de Sodio/química , Antibacterianos/química , Nanoestructuras/química , Cicatrización de Heridas

RESUMEN

Background: Delayed wound healing in skin injuries has become a significant problem in clinics, seriously affecting and even threatening life and health. Recently, research interest has increased in developing wound dressings containing bioactive compounds capable of improving outcomes for complex healing needs. Methods: In this study, Puerarin-loaded nanoparticles (Pue-NPs) were prepared using the cell-penetrating peptide-poly (lactic-co-glycolic acid) (CPP-PLGA) as a drug carrier by the emulsified solvent evaporation method. Then, they were added into poly (acrylic acid) to obtain a self-assembled nanocomposite hydrogels (SANHs) drug delivery system using the co-polymerization method. The particle size, zeta potential, and micromorphology of Pue-NPs were measured; the appearance, mechanical properties, adhesive strength, and biological activity of SANHs were performed. Finally, the potential of SANHs for wound healing was further evaluated in streptozotocin-induced diabetic mice. Results: Pue-NPs were regularly spherical, with an average particle size of 134.57 ± 1.42 nm and a zeta potential of 2.14 ± 0.78 mV. SANHs was colorless and transparent with a honeycomb-like porous structure and had an excellent swelling ratio (917%), water vapor transmission rate (3077 g·m-2·day-1), mechanical properties (Young's modulus of 18 kPa, elongation at break of 307%), and adhesive strength (15.5 kPa). SANHs exhibited sustained release of Pue over 48h, with a cumulative release of 55.60 ± 6.01%. In vitro tests revealed that the SANHs presented a 92.22% antibacterial rate against Escherichia coli after 4h, and a 61.91% scavenging rate of 1.1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical. In vivo experiments showed that SANHs accelerated wound repair by reducing the inflammatory response at the wound site, promoting angiogenesis, and facilitating epidermal regeneration and collagen deposition. Conclusion: In conclusion, we successfully prepared SANHs. Our results show that SANHs have excellent performance and improves wound healing in diabetic mice model, indicating that it can be used to develop an effective strategy for the treatment of diabetic wounds.

Asunto(s)

Diabetes Mellitus Experimental , Nanopartículas , Ratones , Animales , Hidrogeles/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Cicatrización de Heridas , Nanopartículas/química , Antibacterianos/farmacología , Polímeros/farmacología , Péptidos/farmacología

RESUMEN

Injectable hydrogels are receiving increasing attention as local depots for sustained anticancer drug delivery. However, most current hydrogel-based carriers lack tissue-adhesive ability, a property that is important for the immobilization of drug-loaded systems at tumor sites to increase local drug concentration. In this study, we developed a paclitaxel (PTX)-loaded injectable hydrogel with firm tissue adhesion for localized tumor therapy. PTX-loaded bovine serum albumin (BSA) nanoparticles (PTX@BN) were prepared, and the drug-loaded hydrogel was then fabricated by cross-linking PTX@BN with o-phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) via a condensation reaction between OPA and the amines in BSA. The hydrogel showed firm adhesion to various organs and tumor tissues ex vivo due to the condensation reaction of unreacted OPA groups and amines in the tissues. The PTX-loaded nanocomposite hydrogels sustained PTX release over 30 days following the Korsmeyer-Peppas model and exhibited notable inhibition activities against mouse C26 colon and 4T1 breast cancer cells in vitro. Following peritumoral injection into mice with C26 or 4T1 tumors, the PTX@BN-loaded hydrogel significantly enhanced the antitumor efficacy and prolonged animal survival time compared to free PTX solutions with low systemic toxicity. Therefore, the adhesive, PTX-loaded nanocomposite hydrogels have the potential for efficient localized tumor therapy.

Asunto(s)

Hidrogeles , Nanopartículas , Animales , Ratones , Adhesivos , Nanogeles , Línea Celular Tumoral , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Sistemas de Liberación de Medicamentos , Albúminas , Aminas , Portadores de Fármacos , Liberación de Fármacos

RESUMEN

The limitations of traditional therapeutic methods such as chemotherapy serious restricted the application in tumor treatment, including poor targeting, toxic side effects and poor precision. It is important to develop non-chemotherapeutic systems to achieve precise and efficient tumor treatment. Therefore, a functional metal-organic framework material (MOF) with porphyrin core and doped with Cu2+ and surface-modified with polydopamine (PDA), namely PCN-224(Cu)@PDA (PCP) was designed and prepared. After loaded into the injectable and self-healable hydrogels by dynamic Schiff base bonding of oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMC), the multifunctional nanocomposite hydrogels were obtained, in which Cu2+ in MOF converts to Cu+ by reacting with glutathione (GSH) which reduces the tumor antioxidant activity to improve the CDT effect. The Cu2+/Cu+ induces Fenton-like reaction in tumor cells to produce a toxic hydroxyl radical (OH). PDA achieves photothermal conversion under NIR light for photothermal therapy (PTT), and porphyrin core as a ligand generates reactive oxygen species (ROS), presenting highly efficient photodynamic therapy (PDT). Injectable self-healing hydrogel as a loading platform can be in situ injected to tumor site to release PCP and endocytosed by tumor cells to achieve precise and synergistic CDT-PDT-PTT therapy.

Asunto(s)

Quitosano , Nanopartículas , Neoplasias , Porfirinas , Humanos , Nanogeles , Alginatos , Glutatión , Hidrogeles , Óxidos , Línea Celular Tumoral , Peróxido de Hidrógeno