Pluronic F-127 Hydrogel Research Articles

Pluronic F127 coating performance on PLGA nanoparticles: Enhanced flocculation and instability

Nanoparticles (NPs) can be incorporated into hydrogels to obtain multifunctional hybrid systems to meet the delivery needs of different drugs. However, the stability of NPs in hydrogels is rarely revealed. In this article, we tried to explore the underlying mechanism of an interesting phenomenon that poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (PNPs) could flocculate and deposit in Pluronic F127 (F127) hydrogels at 4 °C. The results showed that this flocculation was relevant to the type of emulsifier formulated in PNPs, the particle materials and the F127 concentration, but independent of PLGA polymer end groups. Exactly, PNPs containing polyvinyl alcohol (PVA) as the emulsifier flocculated in F127 solution with a concentration above 15 %. The flocculated PNPs possessed increased particle size, decreased zeta potential, reduced hydrophobicity and an obvious coating layer, and these characteristics could be restored almost to the original state after two washes of flocculated PNPs with water. Moreover, the flocculation had no impact on the long-term size stability and drug-loading capacity of PNPs, and F127-treated PNPs showed improved cellular uptake than untreated PNPs. These results provide the evidence that adsorption of high concentrations of F127 on the surface of PNPs/PVA may lead to flocculation, and the flocculation is reversible by simply washing the flocs with water. To the best of our knowledge, this is the first study to scientifically explore the stability of PNPs in F127 hydrogels, providing theoretical and experimental support for the rational design and further development of nanoparticle-hydrogel composite.

Simple, Rapid, and Large-Scale Fabrication of Multi-Branched Hydrogels Based on Viscous Fingering for Cell Culture Applications.

Hydrogels are widely used in cell culture applications. For fabricating tissues and organs, it is essential to produce hydrogels with specific structures. For instance, multiple-branched hydrogels are desirable for the development of network architectures that resemble the biological vascular network. However, existing techniques are inefficient and time-consuming for this application. To address this issue, a simple, rapid, and large-scale fabrication method based on viscous fingering is proposed. This approach utilizes only two plates. To produce a thin solution, a high-viscosity solution is introduced into the space between the plates, and one of the plates is peeled off. During this procedure, the solution's high viscosity results in the formation of multi-branched structures. Using this strategy, 180mm × 200mm multi-branched Pluronic F-127 hydrogels are successfully fabricated within 1min. These structures are used as sacrificial layers for the fabrication of polydimethylsiloxane channels for culturing human umbilical vein endothelial cells (HUVECs). Similarly, multi-branched Matrigel and calcium (Ca)-alginate hydrogel structures are fabricated, and HUVECs are successfully cultured inside the hydrogels. Also, the hydrogels are collected from the plate, while maintaining their structures. The proposed fabrication technique will contribute to the development of network architectures such as vascular structures in tissue engineering.

Ascidian-Inspired Temperature-Switchable Hydrogels with Antioxidant Fullerenols for Protecting Radiation-Induced Oral Mucositis and Maintaining the Homeostasis of Oral Microbiota.

A key characteristic of radiation-induced oral mucositis (RIOM) is oxidative stress mediated by the "reactive oxygen species (ROS) storm" generated from water radiolysis, resulting in severe pathological lesions, accompanied by a disturbance of oral microbiota. Therefore, a sprayable in situ hydrogel loaded with "free radical sponge" fullerenols (FOH) is developed as antioxidant agent for RIOM radioprotection. Inspired by marine organisms, 3,4,5-trihydroxyphenylalanine (TOPA) which is enriched in ascidians is grafted to clinically approved temperature-switchable Pluronic F127 to produce gallic acid (containing the TOPA fragment)-modified Pluronic F127 (MGA) hydrogels to resist the fast loss of FOH via biomimetic adhesion during oral movement and saliva erosion. Based on this, progressive RIOM found in mice is alleviated by treatment of FOH-loaded MGA hydrogels whether pre-irradiation prophylactic administration or post-irradiation therapeutic administration, which contributes to maintaining the homeostasis of oral microbiota. Mechanistically, FOH inhibits cell apoptosis by scavenging radiation-induced excess ROS and up-regulates the inherent enzymatic antioxidants, thereby protecting the proliferation and migration of mucosal epithelial cells. In conclusion, this work not only provides proof-of-principle evidence for the oral radioprotection of FOH by blocking the "ROS storm", but also provides an effective and easy-to-use hydrogel system for mucosal in situ administration.

PF127 Hydrogel-Based Delivery of Exosomal CTNNB1 from Mesenchymal Stem Cells Induces Osteogenic Differentiation during the Repair of Alveolar Bone Defects.

Pluronic F127 (PF127) hydrogel has been highlighted as a promising biomaterial for bone regeneration, but the specific molecular mechanism remains largely unknown. Herein, we addressed this issue in a temperature-responsive PF127 hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exos) (PF127 hydrogel@BMSC-Exos) during alveolar bone regeneration. Genes enriched in BMSC-Exos and upregulated during the osteogenic differentiation of BMSCs and their downstream regulators were predicted by bioinformatics analyses. CTNNB1 was predicted to be the key gene of BMSC-Exos in the osteogenic differentiation of BMSCs, during which miR-146a-5p, IRAK1, and TRAF6 might be the downstream factors. Osteogenic differentiation was induced in BMSCs, in which ectopic expression of CTNNB1 was introduced and from which Exos were isolated. The CTNNB1-enriched PF127 hydrogel@BMSC-Exos were constructed and implanted into in vivo rat models of alveolar bone defects. In vitro experiment data showed that PF127 hydrogel@BMSC-Exos efficiently delivered CTNNB1 to BMSCs, which subsequently promoted the osteogenic differentiation of BMSCs, as evidenced by enhanced ALP staining intensity and activity, extracellular matrix mineralization (p < 0.05), and upregulated RUNX2 and OCN expression (p < 0.05). Functional experiments were conducted to examine the relationships among CTNNB1, microRNA (miR)-146a-5p, and IRAK1 and TRAF6. Mechanistically, CTNNB1 activated miR-146a-5p transcription to downregulate IRAK1 and TRAF6 (p < 0.05), which induced the osteogenic differentiation of BMSCs and facilitated alveolar bone regeneration in rats (increased new bone formation and elevated BV/TV ratio and BMD, all with p < 0.05). Collectively, CTNNB1-containing PF127 hydrogel@BMSC-Exos promote the osteogenic differentiation of BMSCs by regulating the miR-146a-5p/IRAK1/TRAF6 axis, thus inducing the repair of alveolar bone defects in rats.

Long-lasting postoperative analgesia with local anesthetic-loaded hydrogels prevent tumor recurrence via enhancing CD8+T cell infiltration

Postoperative pain (POP) can promote tumor recurrence and reduce the cancer patient's quality of life. However, POP management has always been separated from tumor treatment in clinical practice, and traditional postoperative analgesia using opioids is still unsatisfactory for patients, which is not conducive to tumor treatment. Here, ropivacaine, a popular amide-type LA, was introduced into a Pluronic F127 hydrogel. Postoperative analgesia with ropivacaine-loaded hydrogels reduced the incidence of high-dose ropivacaine-induced convulsions and prolonged pain relief for more than 16 h. More interestingly, ropivacaine-loaded hydrogel was found to upregulate major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-dopped with ropivacaine and TLR7 agonist imiquimod (PFRM) was rationally synthesized. After postoperative analgesia with PFRM, imiquimod primes tumor-specific CD8+T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+T cells through upregulating MHC-I. Consequently, postoperative analgesia with PFRM maximumly increases CD8+T cells infiltration into residual tumor tissue and prevents tumor recurrence. Overall, this study for the first time provides an LA-based approach for simultaneous long-lasting postoperative analgesia and prevention of tumor recurrence.

Bioactive glass ions hydrogels with antiinflammation antioxidant capacity for treating inflammation-related diseases

Inflammation-related infected wound and rheumatoid arthritis (RA) are still the challenge in biomedical filed. Bioactive molecules and materials are showing much interest in treating inflammation-related diseases. Herein, we report an antiinflammatory antioxidant angiogenetic bioactive ions-based scaffold based on the bioactive nanoglass for treating methicillin-resistant staphylococcus aureus (MRSA) infected wound and RA. It was found that the bioactive nanoglass ions (BNGI) with 3 × and 6 × dilution demonstrated the significant anti-inflammation ability (the inhibition of Tnf-α and IL1β), macrophage polarization function (the decrease of CD86+ cells), antioxidant and angiogenic capacities (the increased node number, branching length and CD31 expression). 1 × diluted BNGI-derived Pluronic F127 and gelatin methacryloyl hydrogels could significantly enhance the MRSA-infected wound healing and attenuate the RA progression through stimulating the secretion of antiinflammation exosomes from macrophage (3-fold upregulation compared with 3MTM dressing) and proper angiogenesis based on the important role of silicon (about 150 mg/L in vivo and 25.4 to 48.1 mg/L in vitro) in BNGI. Our findings revealed the therapeutic function and potential mechanism of BNGI in inflammatory diseases and tissue engineering.

Dipeptide-1 modified nanostructured lipid carrier-based hydrogel with enhanced skin retention and topical efficacy of curcumin.

Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR-DP-NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR-DP-NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR-DP-NLCs had a particle size of 152.6 ± 3.47 nm, a zeta potential of -33.1 ± 1.46 mV, an entrapment efficiency of 99.83 ± 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR-DP-NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR-DP-NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin-eosin staining showed that CUR-DP-NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR-DP-NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR-DP-NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases.

Analgesic and potentiated photothermal therapy with ropivacaine-loaded hydrogels.

Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8+ T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+ T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8+ T cells infiltration into tumor and potentiates PTT efficacy. Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.

Rapid, autonomous high-throughput characterization of hydrogel rheological properties via automated sensing and physics-guided machine learning

High-throughput characterization (HTC) of composition-process-structure-property relations is essential for accelerating molecular and material discovery and manufacturing paradigms. Here, we present a rapid, autonomous method for HTC of hydrogel rheological properties in well plate formats via automated sensing and physics-guided supervised machine learning. The novel HTC method facilitates rapid, autonomous characterization of hydrogel rheological properties and percolation processes associated with gelation and network interpenetration in 96-well plate formats at a rate of 24 s/sample (70 times faster than the state-of-the-art). Viscoelastic properties and phase behavior obtained by the method were benchmarked against traditional rheology studies. The speed and utility of the method were demonstrated by high-resolution characterization of the gel point of Pluronic F127, collagen, and alginate-PNIPAM hydrogels in 96-well plate formats at resolutions of 0.31 wt% (Pluronic F127), 0.031 mg/ml (collagen), and 0.069 wt% (NIPAM), respectively. Experimental composition-property relation data generated from sensor multivariate time-series data, calibration data, and fluid-structure interaction models enabled accurate classification of sample phase using supervised machine learning. Feature augmentation using sensor physics, here, a fluid-structure interaction model, improved material (i.e., sample) phase classification accuracy relative to that obtained in the absence of physics-based feature augmentation. Ultimately, creating rapid, autonomous HTC methods that synergize with common high-throughput experimentation formats, such as well plates, can accelerate the pace of research across several disciplines as well as generate new tools for quality assurance and control across emerging industries.

A topical platelet-independent multilevel clotting initiator for intraoperative hemostasis

Quick and stable clotting is essential in topically controlling intraoperative hemorrhage for patients with chemotherapy-induced thrombocytopenia. Here, we proposed and validated a kind of vesicle originated from gene-engineering cell membrane to manage uncontrolled bleeding with double clotting-triggering strategy. The vesicle constitutively exhibited truncated tissue factor (tTF) protein and phosphatidylserine (PS), thus function as a fibrin growth stimulus and erythrocyte attractant initiator in vitro and in vivo. Erythrocytes assembled in blood clot protected formed fibrin from fibrinolysis while the grown fibrin network enhanced erythrocyte aggregation in situ. Notably, these double clotting-triggering processes worked synergistically to constitute a positive feedback effect to quickly and potently form fibrinolysis-resisted erythrocyte-modified fibrin structures and achieve more stable clotting than the commonly used thrombin and gelatin coagulant. Furthermore, FDA-approved biocompatible Pluronic F127 hydrogel was rationally introduced to assist vesicles depositing onto the wound, thereby maximizing the hemostatic activity and minimizing the postoperative adhesion in a hemorrhage model with cyclophosphamide-induced myelosuppression. This multi-level coagulant method reported here sheds new light on controlling bleeding when patients with myelosuppression undergo surgery.

How to increase the potential of aqueous Zn-MnO2 batteries: The effect of pH gradient electrolyte

Non-rechargeable alkaline Zn-MnO2 batteries are dominating the primary battery market and are a promising candidate for secondary battery storage systems as well. However, these batteries suffer from low potential and poor rechargeability. Here, we report a rechargeable membrane-less amphoteric aqueous Zn-MnO2 battery with a 2.4 V open circuit potential. We have employed alkaline (KOH), acidic (H2SO4) and neutral (K2SO4) Pluronic F-127 hydrogels as electrolytes. By placing the anode in an alkaline environment but the cathode in an acidic environment, we have successfully widened the potential window in an aqueous medium avoiding hydrogen and oxygen evolution reactions. The obtained open circuit potential of as prepared amphoteric battery is stable for more than 25 h and 200 charge-discharge cycles.

Promotion of wound healing by a thermosensitive and sprayable hydrogel with nanozyme activity and anti-inflammatory properties

The rapid healing of wounds requires strategies that relieve oxidative stress resulting from overloaded free radicals and which promote angiogenesis, collagen deposition, and re-epithelialization of the wound. Nickel ions have been reported to be correlated with angiogenesis. However, several applications of metal salts or oxides to wounds lead to increased toxicity. The nickel metal-organic framework (Ni MOF) nanorods described herein can slowly release nickel ions, resulting in reduced toxicity and improved wound healing rates. More importantly, the Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 (Ni3(HITP)2) nanorods with well-defined structures, superior conductivity and many catalytic sites showed superoxide dismutase (SOD)-like enzyme activity and scavenged various free radicals. In addition, the Ni3(HITP)2 nanomaterials contributed to promotion of the migration of fibroblasts, angiogenesis and macrophage polarization from M1 to M2. The aqueous solution of Pluronic F127, a temperature-sensitive, nontoxic and phase-changing hydrogel material, was shown to be an effective choice for injectable and sprayable medical dressings. The Ni3(HITP)2 MOF nanomaterials can be effectively encapsulated with the F127 hydrogel to achieve continuous long-term therapeutic effects. The toxicity test results suggested that the Ni3(HITP)2 MOF nanomaterials exhibited excellent biosafety and no observable toxicity or side effects in mice. Therefore, the Ni3(HITP)2 MOF nanorods hold promising potential in the biomedical field, and this work provides an effective solution to wound therapy.

Structural, rheological and therapeutic properties of pluronic F127 hydrogel and beeswax based lavender oil ointment formulations

Since ancient time, Lavender oil (LO) is being used in aromatherapy as antimicrobial, anxiolytic, analgesic and anti-inflammatory agents. More recently it has been observed that its topical application heals various kinds of wounds by expediting epithelialization and neovascularization processes. Its wound healing characteristics with different delivery systems are however, scarcely reported. The aim of the present study was to evaluate how its healing abilities are manifested when it is applied in the form of beeswax-oil and pluronic F127 hydrogel based ointments. The ointments were prepared by solubilizing or dispersing LO in pluronic F127 hydrogel, beeswax-olive oil, and beeswax-coconut oil based bases. Small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) studies suggest that the prepared ointments are composed of LO solubilized beeswax-oil and F127-water based self- assembled structures. The rheological and spreading properties of the ointments are found to be suitable for topical applications. The ointments do not exhibit any noticeable antimicrobial actions on gram positive and gram negative bacteria presumably due to entrapment of LO within the self-assembled structures formed in them. Studies on efficacies of the ointments on full thickness mice wounds show that healing ability of LO is manifested only from F127 hydrogel in the form of faster epithelialization and neovascularization at the wound site. Such selective manifestation of wound healing efficacies of LO suggests that choice of ointment base is important for effective harnessing of its wound healing abilities.

The effect of resolvin D1 on bone regeneration in a rat calvarial defect model.

Resolvin D1 (RvD1) is a pro-resolving lipid mediator of inflammation, endogenously synthesized from omega-3 docosahexaenoic acid. The purpose of this study was to investigate the effect of RvD1 on bone regeneration using a rat calvarial defect model. Collagen 3D nanopore scaffold (COL) and Pluronic F127 hydrogel (F127) incorporated with RvD1 (RvD1-COL-F127 group) or COL and F127 (COL-F127 group) were implanted in symmetrical calvarial defects. After implantation, RvD1 was administrated subcutaneously every 7days for 4weeks. The rats were sacrificed at weeks 1 and 8 post-implantation. Tissue samples were analyzed by real-time reverse transcriptase-polymerase chain reaction and histology at week 1. Radiographical and histological analyses were done at week 8. At week 1, calvarial defects treated with RvD1 exhibited decreased numbers of inflammatory cells and tartrate-resistant acid phosphatase (TRAP) positive cells, greater numbers of newly formed blood vessels, upregulated gene expression of vascular endothelial growth factor and alkaline phosphatase, and downregulated gene expression of receptor activator of nuclear factor-κB ligand, interleukin-1β and tumor necrosis factor-α. At week 8, the radiographical results showed that osteoid area fraction of the RvD1-COL-F127 group was higher than that of the COL-F127 group, and histological examination exhibited enhanced osteoid formation and newly formed blood vessels in the RvD1-COL-F127 group. In conclusion, this study showed that RvD1 enhanced bone formation and vascularization in rat calvarial defects.

Human adipose-derived mesenchymal stem cells-derived exosomes encapsulated in pluronic F127 hydrogel promote wound healing and regeneration

BackgroundLarge area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originating from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing.MethodshADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis.ResultsCompared with hADSCs-Exos or PF-127 only, PF-127/hADSCs-Exos complexes enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, α-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), up-regulated expression of skin barrier proteins (KRT1, AQP3), and reduced inflammation (IL-6, TNF-α, CD68, CD206). By using PF-127/hADSCs-Exos complexes, hADSCs-Exos can be administrated at lower doses frequency while maintaining the same therapeutic effects.ConclusionAdministration of hADSCs-Exos in PF-127 improves the efficiency of exosome delivery, maintains the bioactivity of hADSCs-Exos, and optimizes the performance of hADSCs-Exos. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds.

Entrega de hidrocloreto de minociclina ativo pelo sistema local de libertação sustentável de hidrogênio complexo e termorresponsivo para cães

ABSTRACT The objective of this study was to develop a novel subgingival sustained-release system for local delivery of bioactive minocycline hydrochloride for periodontal disease treatment in dogs. The system incorporated the Minocycline hydrochloride-Calcium-Dextran sulfate sodium into a thermoresponsive Pluronic F127 hydrogel. Minocycline hydrochloride was sustained release from the system for up to 10 days and the release kinetics fit the power law model. The release medium had a significant statistical difference in antimicrobial activity to Aggregatibacter actinomycetemcomitans. The results showed the system was a promising subgingival sustained-release minocycline hydrochloride delivery system for periodontal disease treatment in dogs.

Bindarit encapsulated nanoparticles prevent venous neointimal hyperplasia and restenosis in a murine angioplasty model

Monocyte and macrophage recruitment occur to the injured vessel wall after percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVF) through increased expression of MCP-1 leading to venous neointimal hyperplasia (VNH) and venous stenosis (VS). We hypothesized that adventitial delivery of Bindarit, an oral selective inhibitor of MCP-1, -2, and -3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (BN NP) could prevent VNH/VS formation in a murine model of PTA with AVF. Scanning electron microscope and dynamic light scattering were used to characterize the BN NP and control nanoparticles (NP C). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to study drug release kinetics. Immediately after PTA, in a murine model of AVF stenosis, BN NP or NP C was administrated to the adventitia of outflow veins. Animals were sacrificed 3 and 21 days later for gene expression, histomorphometric, and immunohistochemical analyses. Doppler ultrasound was performed weekly. There was no difference in the size and storage modulus of BN NP compared to controls. The pharmacokinetic analysis demonstrated increased drug release from BN NP when compared to controls. BN NP-treated vessels had reduced MCP-1, MCP-2, and MCP-3 gene, and protein levels, reduced macrophage/monocyte abundance, proinflammatory cytokines, and venous fibrosis resulting in positive vascular remodeling and improved patency with reduced VNH/VS. There was increased peak velocity 21 days after PTA in the BN NP group. Adventitial administration of BN NP to the outflow vein after PTA results in decreased VNH/VS.

Microwave synthesis of graphene oxide decorated with silver nanoparticles for slow-release antibacterial hydrogel

Inorganic antibacterial materials, graphene oxide (GO), and silver nanoparticles (AgNPs) are considered promising antibacterial materials due to their excellent biocompatibility, broad-spectrum antibacterial properties, and non-drug resistance. In this manuscript, Branched polyethyleneimine (PEI) stabilized GO-AgNPs antibacterial nanocomposites (PEI-GO-AgNPs) were integrated with Pluronic F127 to develop a slow-release antibacterial hydrogel for more stable and sustained antibacterial effect. Antibacterial mechanism has been proposed according to the experimental observation. The synergistic effect of PEI-GO-AgNPs resulted in the death of bacteria and molds. PEI reduced the aggregation of PEI-GO-AgNPs nanomaterials to capture/adsorb pathogens effectively and increased the contact between Ag and pathogens. The sharp edges of the GO nanosheets can physically cut the bacterial cells then the Ag can interact with the cell membrane, disrupting the permeability and material transport of the cell membrane. The antibacterial test showed that the antibacterial rate of 10 μg/mL PEI-GO-AgNPs against bacteria (Escherichia coli) and molds (Candida albicans) are 99.86% and 99.94%. It is worth to mention that the PEI-GO-AgNPs were well dispersed in normal saline within a week. In addition, PEI-GO-AgNPs released 72% Ag from the prepared Pluronic F127 hydrogel within one week.

Methodological Considerations in Development of UV Imaging for Characterization of Intra-Tumoral Injectables Using cAMP as a Model Substance.

A UV imaging release-testing setup comprising an agarose gel as a model for tumorous tissue was developed. The setup was optimized with respect to agarose concentration (0.5% (w/v)), injection procedure, and temperature control. A repeatable injection protocol was established allowing injection into cavities with well-defined geometries. The effective resolution of the SDi2 UV imaging system is 30–80 µm. The linear range of the imaging system is less than that of typical spectrophotometers. Consequently, non-linear cAMP calibration curves were applied for quantification at 280 nm. The degree of deviation from Beer’s law was affected by the background absorbance of the gel matrix. MATLAB scripts provided hitherto missing flexibility with respect to definition and utilization of quantification zones, contour lines facilitating visualization, and automated, continuous data analysis. Various release patterns were observed for an aqueous solution and in situ forming Pluronic F127 hydrogel and PLGA implants containing cAMP as a model for STING ligands. The UV imaging and MATLAB data analysis setup constituted a significant technical development in terms of visualizing behavior for injectable formulations intended for intra-tumoral delivery, and, thereby, a step toward establishment of a bio-predictive in vitro release-testing method.

Chitosan/Pluronic F127 Thermosensitive Hydrogel as an Injectable Dexamethasone Delivery Carrier.

Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.