Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies.

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

Biological activities and possible dental application of three major groups of polyphenols.

The present article reviewed the biological activities and possible dental application of three major polyphenols, i.e., lignin-carbohydrate complexes, tannins, and flavonoids, citing mostly our in vitro studies together with those from other groups. All these polyphenols showed much lower tumor-selective cytotoxicity against oral squamous cell carcinoma cells vs. normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast), in comparison to popular chemotherapeutic antitumor drugs. Several compounds showing higher tumor-selectivity did not induce internucleosomal DNA fragmentation, a biochemical hallmark of apoptosis, in oral carcinoma cell lines. Lignin-carbohydrate complex protected the cells from the cytopathic effects of HIV infection and UV irradiation more efficiently than other polyphenols. Limited digestion of lignin-carbohydrate complex suggests that the lignin moiety is involved in the prominent anti-HIV activity, whereas the carbohydrate moiety may function in immunopotentiating activity through a cell surface receptor. Alkaline extract of plant leaf, which contains higher amounts of lignin-carbohydrate complex, showed potent anti-inflammatory action against IL-1ß-stimulated human gingival fibroblasts. Local application of lignin-carbohydrate complex through oral mucosa is recommended, considering its poor intestinal absorption.

Polyphenol-Mediated Adhesive and Anti-Inflammatory Double-Network Hydrogels for Repairing Postoperative Intervertebral Disc Defects.

Hydrogels have garnered tremendous attention for their applications in the repair of intervertebral disk (IVD) degeneration and postoperative IVD defects. However, it is still challenging to develop a hydrogel fulfilling the requirements for high mechanical properties, adhesive capability, biocompatibility, antibacterial properties, and anti-inflammatory performance. Herein, we report a multifunctional double-network (DN) hydrogel composed of physically cross-linked carboxymethyl chitosan (CMCS) and tannic acid (TA) networks as well as chemically cross-linked acrylamide (AM) networks, which integrates the properties of high strength, adhesion, biocompatibility, antimicrobial activity, and anti-inflammation for the repair of postoperative IVD defects. The treatment with CMCS/TA/PAM DN hydrogels can significantly decrease the levels of inflammatory cytokines and degeneration-related factors and upregulated collagen type II alpha 1. In addition, the hydrogels can effectively seal the annulus fibrosus defect, prevent nucleus pulposus degeneration, retain IVD height, and restore the biomechanical properties of the disc to some extent. This polyphenol-mediated DN hydrogel is promising for sealing IVD defects and preventing herniation after lumbar discectomy.

Recent progress in tannic acid based approaches as a natural polyphenolic biomaterial for cancer therapy: A review.

Significant advancements have been noticed in cancer therapy for decades. Despite this, there are still many critical challenges ahead, including multidrug resistance, drug instability, and side effects. To overcome obstacles of these problems, various types of materials in biomedical research have been explored. Chief among them, the applications of natural compounds have grown rapidly due to their superb biological activities. Natural compounds, especially polyphenolic compounds, play a positive and great role in cancer therapy. Tannic acid (TA), one of the most famous polyphenols, has attracted widespread attention in the field of cancer treatment with unique structural, physicochemical, pharmaceutical, anticancer, antiviral, antioxidant and other strong biological features. This review concentrated on the basic structure along with the important role of TA in tuning oncological signal pathways firstly, and then focused on the use of TA in chemotherapy and preparation of delivery systems including nanoparticles and hydrogels for cancer therapy. Besides, the application of TA/Fe3+ complex coating in photothermal therapy, chemodynamic therapy, combined therapy and theranostics is discussed.

Dual-infinite coordination polymer-engineered nanomedicines for dual-ion interference-mediated oxidative stress-dependent tumor suppression.

Recently, nanomedicine design has shifted from simple nanocarriers to nanodrugs with intrinsic antineoplastic activities for therapeutic performance optimization. In this regard, degradable nanomedicines containing functional inorganic ions have blazed a highly efficient and relatively safe ion interference paradigm for cancer theranostics. Herein, given the potential superiorities of infinite coordination polymers (ICPs) in degradation peculiarity and functional integration, a state-of-the-art dual-ICP-engineered nanomedicine is elaborately fabricated via integrating ferrocene (Fc) ICPs and calcium-tannic acid (Ca-TA) ICPs. Thereinto, Fc ICPs, and Ca-TA ICPs respectively serve as suppliers of ferrous iron ions (Fe2+) and calcium ions (Ca2+). After the acid-responsive degradation of ICPs, released TA from Ca-TA ICPs facilitated the conversion of released ferric iron (Fe3+) from Fc ICPs into highly active Fe2+. Owing to the dual-path oxidative stress and neighboring effect mediated by Fe2+ and Ca2+, such a dual-ICP-engineered nanomedicine effectively induces dual-ion interference against triple-negative breast cancer (TNBC). Therefore, this work provides a novel antineoplastic attempt to establish ICP-engineered nanomedicines and implement ion interference-mediated synergistic therapy.

Biomedical applications of tannic acid.

Tannic Acid (TA) is a naturally occurring antioxidant polyphenol that has gained popularity over the past decade in the field of biomedical research for its unique biochemical properties. Tannic acid, typically extracted from oak tree galls, has been used in many important historical applications. TA is a key component in vegetable tanning of leather, iron gall ink, red wines, and as a traditional medicine to treat a variety of maladies. The basis of TA utility is derived from its many hydroxyl groups and its affinity for forming hydrogen bonds with proteins and other biomolecules. Today, the study of TA has led to the development of many new pharmaceutical and biomedical applications. TA has been shown to reduce inflammation as an antioxidant, act as an antibiotic in common pathogenic bacterium, and induce apoptosis in several cancer types. TA has also displayed antiviral and antifungal activity. At certain concentrations, TA can be used to treat gastrointestinal disorders such as hemorrhoids and diarrhea, severe burns, and protect against neurodegenerative diseases. TA has also been utilized in biomaterials research as a natural crosslinking agent to improve mechanical properties of natural and synthetic hydrogels and polymers, while also imparting anti-inflammatory, antibacterial, and anticancer activity to the materials. TA has also been used to develop thin film coatings and nanoparticles for drug delivery. In all, TA is fascinating molecule with a wide variety of potential uses in pharmaceuticals, biomaterials applications, and drug delivery strategies.

An All-in-One Tannic Acid-Containing Hydrogel Adhesive with High Toughness, Notch Insensitivity, Self-Healability, Tailorable Topography, and Strong, Instant, and On-Demand Underwater Adhesion.

Hydrogels that are mechanically tough and capable of strong underwater adhesion can lead to a paradigm shift in the design of adhesives for a variety of biomedical applications. We hereby innovatively develop a facile but efficient strategy to prepare hydrogel adhesives with strong and instant underwater adhesion, on-demand detachment, high toughness, notch-insensitivity, self-healability, low swelling index, and tailorable surface topography. Specifically, a polymerization lyophilization conjugation fabrication method was proposed to introduce tannic acid (TA) into the covalent network consisting of polyethylene glycol diacrylate (PEGDA) of substantially high molecular weight. The presence of TA facilitated wet adhesion to various substrates by forming collectively strong noncovalent bonds and offering hydrophobicity to allow water repellence and also provided a reversible cross-link within the binary network to improve the mechanical performance of the gels. The long-chain PEGDA enhanced the efficacy and stability of TA conjugation and contributed to gel mechanics and adhesion by allowing chain diffusion and entanglement formation. Moreover, PEGDA/TA hydrogels were demonstrated to be biocompatible and capable of accelerating wound healing in a skin wound animal model as compared to commercial tissue adhesives and can be applied for the treatment of both epidermal and intracorporeal wounds. Our study provides new, critical insight into the design principle of all-in-one hydrogels with outstanding mechanical and adhesive properties and can potentially enhance the efficacy of hydrogel adhesives for wound healing.

Universal Antifouling and Photothermal Antibacterial Surfaces Based on Multifunctional Metal-Phenolic Networks for Prevention of Biofilm Formation.

Biofilms formed from the pathogenic bacteria that attach to the surfaces of biomedical devices and implantable materials result in various persistent and chronic bacterial infections, posing serious threats to human health. Compared to the elimination of matured biofilms, prevention of the formation of biofilms is expected to be a more effective way for the treatment of biofilm-associated infections. Herein, we develop a facile method for endowing diverse substrates with long-term antibiofilm property by deposition of a hybrid film composed of tannic acid/Cu ion (TA/Cu) complex and poly(ethylene glycol) (PEG). In this system, the TA/Cu complex acts as a multifunctional building block with three different roles: (i) as a versatile "glue" with universal adherent property for substrate modification, (ii) as a photothermal biocidal agent for bacterial elimination under irradiation of near-infrared (NIR) laser, and (iii) as a potent linker for immobilization of PEG with inherent antifouling property to inhibit adhesion and accumulation of bacteria. The resulted hybrid film shows negligible cytotoxicity and good histocompatibility and could prevent biofilm formation for at least 15 days in vitro and suppress bacterial infection in vivo, showing great potential for practical applications to solve the biofilm-associated problems of biomedical materials and devices.

Chitosan/gelatin-tannic acid decorated porous tape suture with multifunctionality for tendon healing.

The inferior tendon healing after surgery is inextricably linked to the surgical suture. Poor load transfer along the suture often results in a high tendon re-tear rate. Besides, the severe inflammation and infection induced by sutures even cause a second surgery. Herein, to alleviate the above-mentioned issues, a multifunctional suture was fabricated by decorating chitosan/gelatin-tannic acid (CS/GE-TA) on the porous tape suture. The porous tape suture ensured the required mechanical properties and sufficient space for tissue integration. Compared to the pristine suture, the CS/GE-TA decorated suture (TA100) presented a 332% increase in pull-out force from the tendon, indicating potentially decreased re-tear rates. Meanwhile, TA100 showed superior anti-inflammatory and antibacterial performances. In vivo experiments further proved that TA100 could not only reduce inflammatory action but also facilitate collagen deposition and blood vessel formation. These results indicate that the multifunctional sutures are promising candidates for accelerating tendon healing.

Anthelmintic activity of some Mediterranean browse plants against parasitic nematodes.

The anthelmintic properties of tannin-rich plants are being explored as an alternative to chemical drugs. Most data have been acquired on legume forages, but only few on browse plants. The present study aimed to (i) screen the in vitro effects of extracts from 7 Mediterranean plants on Haemonchus contortus, (ii) verify the role of tannins using an inhibitor, polyvinyl polypyrrolidone (PVPP) and (iii) verify the in vivo effects of extracts from 4 plants. Significant inhibition was shown in vitro using a larval migration inhibition (LMI) assay for all extracts except that from Olea europaea var. koroneiki. After adding PVPP, the LMI values were restored to control levels for all plants except Pistacia lentiscus and Ceratonia siliqua, confirming a role for tannins in the activity. In the in vivo experiment, 48 lambs composed 6 groups, depending on diet. On Day 0, groups G1-G5 received H. contortus and Trichostrongylus colubriformis larvae and G6 remained uninfected. The various diets were distributed from Days 14 to 45: P. lentiscus (G1), Quercus coccifera (G2), C. siliqua (G3), Onobrychis viciifolia (G4), or Medicago sativa for the 2 control groups (G5, G6). Egg excretion, packed cell volumes (PCVs) and inorganic phosphate were measured weekly throughout the entire experimental period. At slaughter, the worms were enumerated and their fecundity assessed. Consumption of the 4 browser plants did not provoke differences in pathophysiological measurements but there were significant decreases in egg excretion, mainly explained by significant decreases in worm fecundity for both species, without any statistical difference in worm numbers.

Tannic Acid Inhibits Non-small Cell Lung Cancer (NSCLC) Stemness by Inducing G0/G1 Cell Cycle Arrest and Intrinsic Apoptosis.

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is one among the most common cancers worldwide. Recently, dietary phytochemicals have been reported as an attractive approach to improve the symptoms of NSCLC patients. Tannic acid is a natural polyphenol, which is known to have anticancer effects on in vitro models of breast, gingival and colon cancer. However, the molecular mechanisms associated with the actions of tannic acid on A549 human lung cancer cells have not been elucidated. MATERIALS AND METHODS: In this study, we analyzed the effect of tannic acid on A549 cells and their underlying mechanisms using western blotting, flow cytometry, invasion assay and tumorsphere formation assay. RESULTS: Tannic acid treatment suppressed the viability of A549 cells through cell cycle arrest and induction of the intrinsic pathways of apoptosis. In addition, the various malignant phenotypes of A549 cells including invasion, migration, and stemness were inhibited by tannic acid treatment. CONCLUSION: Tannic acid could be used as an effective inhibitor of lung cancer progression.

A sustained zero-order release carrier for long-acting, peakless basal insulin therapy.

Basal insulin therapy plays a key role in diabetes management. An ideal therapy should mimic the steady physiologic basal insulin secretion, and provide a peak-free, prolonged and steady insulin supply. Herein, a new drug carrier was designed by first PEGylating insulin and then incorporating the conjugate into layer-by-layer assembled films with tannic acid (TA). Because PEG-insulin and TA in the films were linked with reversible, dynamic hydrogen bonds, the films disintegrate gradually when soaked in aqueous solutions, and thus release PEG-insulin into the media. In vitro release tests revealed that the release of PEG-insulin follows a zero-order kinetics. Theoretical analysis based on the unique release mechanism also supports a zero-order kinetics. In vivo tests using a streptozotocin-induced diabetic rat model demonstrated that subcutaneous implantation of the film could maintain a steady plasma drug level and hence maintain a fasting blood glucose level (BGL) close to normal. The duration of action depends on the thickness of the film. Using a 50-bilayer film, fasting BGL was kept within the normoglycemic range for ∼16 days. Initial burst release, a severe problem for other release systems, was successfully avoided.

Thermosensitive and pH-responsive tannin-containing hydroxypropyl chitin hydrogel with long-lasting antibacterial activity for wound healing.

Polysaccharide hydrogels have been widely used as wound dressings because of their biocompatibility and ability to provide moist environment for wound healing. However, bacterial infection often delays the healing process. Herein, a novel thermosensitive and pH-sensitive hydroxypropyl chitin/tannic acid/ferric ion (HPCH/TA/Fe) composite hydrogel was fabricated by a simple assembly. The pre-cooled hydrogel precursor solution can be injected onto the irregular wound area and gel rapidly at physiological temperature. The TA not only acted as a crosslinker to enhance mechanical properties of the hydrogel, but also as an antibacterial agent which could be sustainably released in response to the acidic environment. The composite hydrogel showed excellent broad-spectrum antibacterial activity up to 7 days with negligible cytotoxicity. Moreover, the hydrogel can inhibit bacterial infection and accelerate the wound healing process without scars in the mouse experiment. These results indicate the potential application of this composite hydrogel for the infected wound healing.

Biguanide-Derived Polymeric Nanoparticles Kill MRSA Biofilm and Suppress Infection In Vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of drug-resistant infections. Its propensity to develop biofilms makes it especially resistant to conventional antibiotics. We present a novel nanoparticle (NP) system made from biocompatible F-127 surfactant, tannic acid (TA), and biguanide-based polymetformin (PMET) (termed FTP NPs), which can kill MRSA biofilm bacteria effectively in vitro and in vivo and which has excellent biocompatibility. FTP NPs exhibit biofilm bactericidal activity-ability to kill bacteria both inside and outside biofilm-significantly better than many antimicrobial peptides or polymers. At low concentrations (8-32 µg/mL) in vitro, FTP NPs outperformed PMET with ∼100-fold (∼2 log10) greater reduction of MRSA USA300 biofilm bacterial cell counts, which we attribute to the antifouling property of the hydrophilic poly(ethylene glycol) contributed by F-127. Further, in an in vivo murine excisional wound model, FTP NPs achieved 1.8 log10 reduction of biofilm-associated MRSA USA300 bacteria, which significantly outperformed vancomycin (0.8 log10 reduction). Moreover, in vitro cytotoxicity tests showed that FTP NPs have less toxicity than PMET toward mammalian cells, and in vivo intravenous injection of FTP NPs at 10 mg/kg showed no acute toxicity to mice with negligible body weight loss and no significant perturbation of blood biomarkers. These biguanide-based FTP NPs are a promising approach to therapy of MRSA infections.

Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.

Soft Conducting Polymer Hydrogels Cross-Linked and Doped by Tannic Acid for Spinal Cord Injury Repair.

Mimicking soft tissue mechanical properties and the high conductivity required for electrical transmission in the native spinal cord is critical in nerve tissue regeneration scaffold designs. However, fabricating scaffolds of high conductivity, tissue-like mechanical properties, and excellent biocompatibility simultaneously remains a great challenge. Here, a soft, highly conductive, biocompatible conducting polymer hydrogel (CPH) based on a plant-derived polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord injury (SCI). The developed hydrogels exhibit an excellent electronic conductivity (0.05-0.18 S/cm) and appropriate mechanical properties (0.3-2.2 kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with a higher conductivity accelerated the differentiation of neural stem cells (NSCs) into neurons while suppressing the development of astrocytes. In vivo, with relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in the lesion area, resulting in significant recovery of locomotor function. Overall, our findings evidence that the CPHs without being combined with any other therapeutic agents have stimulated tissue repair following an SCI and thus have important implications for future biomaterial designs for SCI therapy.

Effects of green tea (Camellia sinensis) mouthwash containing 1% tannin on dental plaque and chronic gingivitis: a double-blinded, randomized, controlled trial.

AIM: The aim of the present study was to explore the effects of Iranian green tea mouthwash containing 1% tannin on dental plaque and chronic gingivitis. METHODS: In this randomized, double-blinded, parallel, controlled clinical trial, 40 volunteer dental students with a gingival index ≥1 were enrolled. At baseline, gingival, plaque, and bleeding indices were recorded and all the participants received dental polishing. Based on random allocation, 20 participants used the test and 20 used chlorhexidine mouthwash with no change in regular toothbrushing methods. The participants were asked to use 15 mL of the respective mouthwash for 1 min, twice a day for 28 days. All indices, as well as stain index, were recorded after 1 and 4 weeks post-rinsing. Data were analyzed using repeated-measures ANOVA and Bonferroni tests. RESULTS: Significant in-group differences, but not between-group differences, were observed in all indices after 1 and 4 weeks compared to baseline. The test mouthwash resulted in significantly less tooth staining than the control. CONCLUSION: The 1% tannin green tea mouthwash could be a safe and feasible adjunct to mechanical plaque control. The tested green tea mouthwash could be considered a good alternative for chlorhexidine in contraindicating situations.

Modified xanthan gum for buccal delivery-A promising approach in treating sialorrhea.

AIM: The aim of this study was to modify xanthan, a well-known gelling agent, in order to treat sialorrhea, which increases salivary flow due to an excessive stimulus of the salivary reflex. METHODS: Chemical modification occurs by covalent attachment of l-cysteine (SH) to the polymeric backbone of xanthan (X) via amide bond formation. Safety considerations, water uptake capacity, and erosion were evaluated. Furthermore, mucoadhesiveness on buccal mucosa and vapor uptake studies were performed. In vitro/in vivo correlation of reduce of salivary flow was conducted and drug release of embedded tannin was determined. RESULTS: Safety investigations ensured modified X-SH being safe to use. X-SH exposed 1.5-x higher water uptake capacity in comparison to unmodified xanthan. Then, stability of X-SH augmented 5.5-fold in the case of matrix erosion studies. Reduction of salivary flow could be obtained 1.6-fold improved in case of X-SH compared to X. Furthermore, tannin was 1.8-fold controlled released in comparison to unmodified xanthan. CONCLUSION: Taking these findings into consideration, chemical modified xanthan emerged with its distinctive properties as a promising approach in treating sialorrhea.

[A clinico-pharmacological study of olifen in periodontal inflammation]. / Kliniko-farmakologicheskoe izuchenie olifena pri vospalenii øarodonta.

Clinical study of the efficacy of oliphen treatment in generalized periodontitis in comparison with galascorbin treatment was conducted. Oliphen arrested the inflammatory process in the periodontium quickly and effectively and shortened the duration of treatment by half. Under its effect lipid peroxidation became less intense, the level of malonic dealdehyde decreased, and the activity of catalase in the oral fluid of patients with periodontitis increased. The favorable effect of oliphen in periodontitis is connected with its antioxidant and antihypoxant properties.

[Clinical studies on crevicular fluid of abutment tooth. 3. Effect of tannin-fluoride preparation on gingival health].

It was examined, in this study, whether the tannin-fluoride preparation (HY preparation), which might have a caries reductive, plaque inhibiting and astringent action, could reduce the incidence of gingival inflammation around abutment teeth for removable partial dentures. Zinc oxide eugenol cement mixed with HY preparation filled in the cavity prepared in the resin base facing the abutment tooth. Crevicular fluid (Periotron unit: GCF), gingival index (GI), plaque index (PII), probing depth and caries activity around the abutment tooth were measured during 12 months. The following results were obtained: 1. GCF decreased at 1 month later and showed low values at 2, 3, 6 and 12 months. 2. The percentage of low GI value showed an increasing tendency during the experimental period. 3. There was slight variation in PII and probing depth during the experimental period. 4. Caries activity showed a decreasing tendency. These results indicate that the tannin-fluoride preparation reduces not only caries activity but also gingival inflammation around abutment tooth.