Antiviral Effects of Secondary Metabolites from Jatropha podagrica Leaves against the Pseudotyped Virus of SARS-CoV-2 Omicron.

Jatropha podagrica holds a longstanding place in traditional herbal medicine, primarily utilized for addressing skin infections, acting as antipyretics, diuretics, and purgatives. In this study, our primary objective was to investigate the secondary metabolites present in J. podagrica leaves, with the aim of pinpointing natural compounds exhibiting potential antiviral activities. Five secondary metabolites (1-5), including an auronol glycoside (1), two coumarins (2 and 3), a chromane (4) and a gallotannin (5), were isolated from J. podagrica leaves. Compound 1 presented as an amalgamation of unseparated mixtures, yet its intricate composition was adroitly unraveled through the strategic deployment of a chiral HPLC column. This tactic yielded the isolation of epimers (+)-1 and (-)-1, ascertained as unreported auronol glycosides. The structures of these novel compounds, (+)-1 and (-)-1, were elucidated to be (2S)-hovetrichoside C [(+)-1] and (2R)-hovetrichoside C [(-)-1] through NMR data and HR-ESIMS analyses, enzymatic hydrolysis, and comparison of optical rotation values. Cytotoxicity and antiviral effects were assessed for the isolated compounds ((+)-1, (-)-1 and 2-5), along with compound 1a (the aglycone of 1), in the A549 human alveolar basal epithelial cell line. Each compound demonstrated a cell viability of approximately 80% or higher, confirming their non-toxic nature. In the group of compounds, compounds 3-5 demonstrated antiviral effects based on RT-qPCR results, with individual enhancements ranging from approximately 28 to 38%. Remarkably, compound 4 exhibited the most substantial antiviral effect. Utilization of compound 4 to assess immune boosting and anti-inflammatory effects revealed increased levels of STING, RIG-I, NLRP3, and IL-10 along with a decrease in TNF-α and IL-6. Therefore, these findings underscore the potential of these active compounds 3-5 not only as therapeutic agents for SARS-CoV-2 but also as new contenders for upcoming pandemics.

Global Natural Products Social (GNPS)-Based Molecular-Networking-Guided Isolation of Phenolic Compounds from Ginkgo biloba Fruits and the Identification of Estrogenic Phenolic Glycosides.

Ginkgo biloba L. stands as one of the oldest living tree species, exhibiting a diverse range of biological activities, including antioxidant, neuroprotective, anti-inflammatory, and cardiovascular activities. As part of our ongoing discovery of novel bioactive components from natural sources, we directed our focus toward the investigation of potential bioactive compounds from G. biloba fruit. The profiles of its chemical compounds were examined using a Global Natural Products Social (GNPS)-based molecular networking analysis. Guided by this, we successfully isolated and characterized 11 compounds from G. biloba fruit, including (E)-coniferin (1), syringin (2), 4-hydroxybenzoic acid 4-O-ß-D-glucopyranoside (3), vanillic acid 4-O-ß-D-glucopyranoside (4), syringic acid 4-O-ß-D-glucopyranoside (5), (E)-ferulic acid 4-O-ß-D-glucoside (6), (E)-sinapic acid 4-O-ß-D-glucopyranoside (7), (1'R,2'S,5'R,8'S,2'Z,4'E)-dihydrophaseic acid 3'-O-ß-D-glucopyranoside (8), eucomic acid (9), rutin (10), and laricitrin 3-rutinoside (11). The structural identification was validated through a comprehensive analysis involving nuclear magnetic resonance (NMR) spectroscopic data and LC/MS analyses. All isolated compounds were evaluated using an E-screen assay for their estrogen-like effects in MCF-7 cells. As a result, compounds 2, 3, 4, 8, and 9 promoted cell proliferation in MCF-7 cells, and these effects were mitigated by the ER antagonist, ICI 182,780. In particular, cell proliferation increased most significantly to 140.9 ± 6.5% after treatment with 100 µM of compound 2. The mechanism underlying the estrogen-like effect of syringin (2) was evaluated using a Western blot analysis to determine the expression of estrogen receptor α (ERα). We found that syringin (2) induced an increase in the phosphorylation of ERα. Overall, these experimental results suggest that syringin (2) can potentially aid the control of estrogenic activity during menopause.

A Comparative Study of Gamma-Ray Irradiation-Induced Oxidation: Polyethylene, Poly (Vinylidene Fluoride), and Polytetrafluoroethylene.

Radiation techniques are used to modify the physical, chemical and biological properties of polymers. This induces crosslinking and degradation reactions of polymers by utilizing radicals generated through ionizing radiation. However, oxidation products (such as carbonyl) can be formed because oxidation occurs by chain scission in the presence of oxygen. Herein, we demonstrate the gamma-ray irradiation-induced oxidation with and without fluorine using polyethylene, polyvinylidene fluoride and polytetrafluoroethylene under the same conditions. In this study, changes in element-content and chemical-bond structures were analyzed before and after gamma-ray irradiation under air atmosphere. As a result, polytetrafluo-roethylene showed less oxidation and excellent thermal properties after the absorbed dose of 500 kGy. This can be attributed to the generation of stable perfluoroalkylperoxy radicals after gamma ray irradiation in the PTFE structure containing only CF2 groups, thereby hindering the oxidation reaction.

New damage model for simulating radiation-induced direct damage to biomolecular systems and experimental validation using pBR322 plasmid.

In this work, we proposed a new damage model for estimating radiation-induced direct damage to biomolecular systems and validated its the effectiveness for pBR322 plasmids. The proposed model estimates radiation-induced damage to biomolecular systems by: (1) simulation geometry modeling using the coarse-grained (CG) technique to replace the minimum repeating units of a molecule with a single bead, (2) approximation of the threshold energy for radiation damage through CG potential calculation, (3) calculation of cumulative absorption energy for each radiation event in microscopic regions of CG models using the Monte Carlo track structure (MCTS) code, and (4) estimation of direct radiation damage to biomolecular systems by comparing CG potentials and absorption energy. The proposed model replicated measured data with an average error of approximately 14.2% in the estimation of radiation damage to pBR322 plasmids using the common MCTS code Geant4-DNA. This is similar to the results of previous simulation studies. However, in existing damage models, parameters are adjusted based on experimental data to increase the reliability of simulation results, whereas in the proposed model, they can be determined without using empirical data. Because the proposed model proposed is applicable to DNA and various biomolecular systems with minimal experimental data, it provides a new method that is convenient and effective for predicting damage in living organisms caused by radiation exposure.

Evaluation of Radiation Resistance of Polystyrene Using Molecular Dynamics Simulation.

The scission rates of polystyrene and fluorinated polystyrene irradiated in an irradiation facility with Co-60 γ-rays were determined using molecular dynamics simulation and gel permeation chromatography (GPC) molecular weight distributions. The prediction was based on the assumption that γ-ray energy is transferred to the initial velocity of the primary knock-on atom. We employed a molecular dynamics simulation procedure to compute the changes in bond length between the connections for selected values of the absorbed dose and compared the calculated values with measurements made on the irradiated samples. The samples were exposed to four different absorbed doses of 25, 50, 75, and 100 kGy. The scission process and scission ratio were simulated with LAMMPS with ReaxFF potential for each bond, and we compared the simulation results with the experimental data especially measuring average molecular weight to evaluate the effect of fluorination on radiation enhancement.

Preliminary Study on the Simulation of a Radiation Damage Analysis of Biodegradable Polymers.

In this study, biodegradable poly(L-lactide-co-ε-caprolactone) (PLCL) and poly(L-co-d,l lactide) (PLDLA) were evaluated using Geant4 (G4EmStandardPhysics_option4) for damage simulation, in order to predict the safety of these biodegradable polymers against gamma ray sterilization. In the PLCL damage model, both chain scission and crosslinking reactions appear to occur at a radiation dose in the range 0-200 kGy, but the chain cleavage reaction is expected to be relatively dominant at high irradiation doses above 500 kGy. On the other hand, the PLDLA damage model predicted that the chain cleavage reaction would prevail at the total irradiation dose (25-500 kGy). To verify the simulation results, the physicochemical changes in the irradiated PLCL and PLDLA films were characterized by GPC (gel permeation chromatography), ATR-FTIR (attenuated total reflection Fourier transform infrared), and DSC (difference scanning calorimetry) analyses. The Geant4 simulation curve for the radiation-induced damage to the molecular weight was consistent with the experimentally obtained results. These results imply that the pre-simulation study can be useful for predicting the optimal irradiation dose and ensuring material safety, particularly for implanted biodegradable materials in radiation processing.

Quantitative Photothermal Characterization with Bioprinted 3D Complex Tissue Constructs for Early-Stage Breast Cancer Therapy Using Gold Nanorods.

Plasmonic photothermal therapy (PPTT) using gold nanoparticles (AuNPs) has shown great potential for use in selective tumor treatment, because the AuNPs can generate destructive heat preferentially upon irradiation. However, PPTT using AuNPs has not been added to practice, owing to insufficient heating methods and tissue temperature measurement techniques, leading to unreliable and inaccurate treatments. Because the photothermal properties of AuNPs vary with laser power, particle optical density, and tissue depth, the accurate prediction of heat generation is indispensable for clinical treatment. In this report, bioprinted 3D complex tissue constructs comprising processed gel obtained from porcine skin and human decellularized adipose tissue are presented for characterization of the photothermal properties of gold nanorods (AuNRs) having an aspect ratio of 3.7 irradiated by a near-infrared laser. Moreover, an analytical function is suggested for achieving PPTT that can cause thermal damage selectively on early-stage human breast cancer by regulating the heat generation of the AuNRs in the tissue.

Self-Aggregation-Controlled Rapid Chemical Bath Deposition of SnO2 Layers and Stable Dark Depolarization Process for Highly Efficient Planar Perovskite Solar Cells.

Planar perovskite solar cells (PSCs) incorporating n-type SnO2 have attracted significant interest because of their excellent photovoltaic performance. However, the film fabrication of SnO2 is limited by self-aggregation and inhomogeneous growth of the intermediate phase, which produces poor morphology and properties. In this study, a self-controlled SnO2 layer is fabricated directly on a fluorine-doped tin oxide (FTO) surface through simple and rapid chemical bath deposition. The PSCs based on this hydrolyzed SnO2 layer exhibit an excellent power conversion efficiency of 20.21 % with negligible hysteresis. Analysis of the electrochemical impedance spectroscopy on the charge transport dynamics indicates that the bias voltage influences both interfacial charge transportation and the ionic double layer under illumination. The hydrolyzed SnO2 -based PSCs demonstrate a faster ionic charge response time of 2.5 ms in comparison with 100.5 ms for the hydrolyzed TiO2 -based hysteretic PSCs. The results of quasi-steady-state carrier transportation indicate that a dynamic hysteresis in the J-V curves can be explained by complex ionic-electronic kinetics owing to the slow ionic charge redistribution and hole accumulation caused by electrode polarization, which causes an increase in charge recombination. This study reveals that SnO2 -based PSCs lead to a stabilized dark depolarization process compared with TiO2 -based PSCs, which is relevant to the charge transport dynamics in the high-performing planar SnO2 -based PSCs.

Preparation and evaluation of ß-glucan hydrogel prepared by the radiation technique for drug carrier applications.

ß-Glucan can provide excellent environment to apply to drug carrier due to its immunological and anti-inflammatory effect. Minocycline hydrochloride (MH) has excellent oral bioavailability pharmacological properties. Specifically, MH is effectively absorbed into the gingiva for periodontal disease treatment. In this study, we attempt to develop MH loaded ß-glucan hydrogel for periodontal disease treatment through radiation-crosslinking technique. In addition, MH loaded ß-glucan hydrogels were tested for their cytotoxicity and antibacterial activity. Finally, we conducted an in vivo study to demonstrate the potential to prevent the invasion of bacteria to treat periodontal disease. The gel content and compressive strength of the ß-glucan hydrogels increased as the ß-glucan content and the absorbed dose (up to 7 kGy) increased. For a radiation dose of 7 kGy, the gelation and the compressive strength of a 6 wt% ß-glucan hydrogel were approximately 92% and 270 kPa, respectively. As a drug, MH was consistently released from ß-glucan hydrogels, reaching 80% at approximately 90 min. Furthermore, the MH loaded ß-glucan hydrogels showed no cytotoxicity. The MH loaded ß-glucan hydrogels exhibited good antibacterial activity against Porphyromonas gingivalis. In addition, MH loaded ß-glucan hydrogel demonstrated the potential of a good capability to prevent the invasion of bacteria and to treat wounds.

Effective gamma-ray sterilization and characterization of conductive polypyrrole biomaterials.

Conductive polymers, including polypyrrole (PPy), have been extensively explored to fabricate electrically conductive biomaterials for bioelectrodes and tissue engineering scaffolds. For their in vivo uses, a sterilization method without severe impairment of original material properties and performance is necessary. Gamma-ray radiation has been commonly applied for sterilization of medical products because of its simple and uniform sterilization without heat generation. Herein we describe the first study on gamma-ray sterilization of PPy bioelectrodes and its effects on their characteristics. We irradiated PPy bioelectrodes with different doses (0-75 kGy) of gamma-rays. Gamma-ray irradiation of the PPy (γ-PPy) increased the oxygenation and hydrophilicity of the surfaces. Interestingly, gamma-ray irradiation did not alter the electrical impedances and conductivities of the PPy substrates. Additionally, γ-PPy prepared with various dopants (e.g., para-toluene sulfonate, polystyrene sulfonate, and chlorine) showed the electrochemical properties similar to the non-irradiated control. Gamma-ray irradiation at doses of ≥15 kGy was required for effective sterilization as evidenced by complete eradication of gram positive and negative bacteria. γ-PPy substrates also showed cytocompatibility similar to untreated control PPy, indicating no substantial alteration of cytocompatibility. In conclusion, gamma ray sterilization is a viable method of sterilization of conducting polymer-based biomaterials for biomedical applications.

One-step synthesis of gene carrier via gamma irradiation and its application in tumor gene therapy.

INTRODUCTION: Although numerous studies have been conducted with the aim of developing drug-delivery systems, chemically synthesized gene carriers have shown limited applications in the biomedical fields due to several problems, such as low-grafting yields, undesirable reactions, difficulties in controlling the reactions, and high-cost production owing to multi-step manufacturing processes. MATERIALS AND METHODS: We developed a 1-step synthesis process to produce 2-aminoethyl methacrylate-grafted water-soluble chitosan (AEMA-g-WSC) as a gene carrier, using gamma irradiation for simultaneous synthesis and sterilization, but no catalysts or photoinitiators. We analyzed the AEMA graft site on WSC using 2-dimensional nuclear magnetic resonance spectroscopy (2D NMR; 1H and 13C NMR), and assayed gene transfection effects in vitro and in vivo. RESULTS: We revealed selective grafting of AEMA onto C6-OH groups of WSC. AEMA-g-WSC effectively condensed plasmid DNA to form polyplexes in the size range of 170 to 282 nm. AEMA-g-WSC polyplexes in combination with psi-hBCL2 (a vector expressing short hairpin RNA against BCL2 mRNA) inhibited tumor cell proliferation and tumor growth in vitro and in vivo, respectively, by inducing apoptosis. CONCLUSION: The simple grafting process mediated via gamma irradiation is a promising method for synthesizing gene carriers.

Preparation and Characterization of Resorbable Bacterial Cellulose Membranes Treated by Electron Beam Irradiation for Guided Bone Regeneration.

Bacterial cellulose (BC) is an excellent biomaterial with many medical applications. In this study, resorbable BC membranes were prepared for guided bone regeneration (GBR) using an irradiation technique for applications in the dental field. Electron beam irradiation (EI) increases biodegradation by severing the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used to determine optimal electron beam doses. Electron beam irradiated BC membranes (EI-BCMs) were evaluated by scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, thermal gravimetric analysis (TGA), and using wet tensile strength measurements. In addition, in vitro cell studies were conducted in order to confirm the cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k EI-BCMs (100 kGy and 300 kGy irradiated BC membranes) were significantly greater than on NI-BCMs after 3 and 7 days (p < 0.05). Bone regeneration by EI-BCMs and their biodegradabilities were also evaluated using in vivo rat calvarial defect models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited significantly larger new bone area (NBA; %) than 300k EI-BCMs at 8 weeks after implantation (p < 0.05). Mechanical, chemical, and biological analyses showed EI-BCMs effectively interacted with cells and promoted bone regeneration.

The Effect of Thickness of Resorbable Bacterial Cellulose Membrane on Guided Bone Regeneration.

This study introduces the effect of the thickness of a bacterial cellulose membrane by comparing the bone regeneration effect on rat skulls when using a collagen membrane and different thicknesses of resorbable bacterial cellulose membranes for guided bone regeneration. Barrier membranes of 0.10 mm, 0.15 mm, and 0.20 mm in thickness were made using bacterial cellulose produced as microbial fermentation metabolites. Mechanical strength was investigated, and new bone formation was evaluated through animal experimental studies. Experimental animals were sacrificed after having 2 weeks and 8 weeks of recovery, and specimens were processed for histologic and histomorphometric analyses measuring the area of bone regeneration (%) using an image analysis program. In 2 weeks, bone-like materials and fibrous connective tissues were observed in histologic analysis. In 8 weeks, all experimental groups showed the arrangement of osteoblasts surrounding the supporting body on the margin and center of the bone defect region. However, the amount of new bone formation was significantly higher (p < 0.05) in bacterial cellulose membrane with 0.10 mm in thickness compared to the other experimental groups. Within the limitations of this study, a bacterial cellulose membrane with 0.10 mm thickness induced the most effective bone regeneration.

Chestnut Honey Impregnated Carboxymethyl Cellulose Hydrogel for Diabetic Ulcer Healing.

Honey-based wound dressings have attracted a lot of attention from modern scientists owing to their anti-inflammatory and antibacterial effects without antibiotic resistance. Such dressings also promote moist wound healing, and have been considered natural, abundant, and cheap materials for folk marketing. This study investigated the various behaviors and characteristics of chestnut honey-impregnated carboxymethyl cellulose sodium hydrogel paste (CH⁻CMC) as a therapeutic dressing, such as its moist retention, antibacterial activity for inhibiting the growth of Staphylococcus aureus and Escherichia coli, and the rate of wound healing in db/db mice. The results provide good evidence, suggesting that CH⁻CMC has potential as a competitive candidate for diabetic ulcer wound healing.

Engineered ECM-like microenvironment with fibrous particles for guiding 3D-encapsulated hMSC behaviours.

The alginate hydrogel has been used as an attractive scaffold for tissue regeneration. In particular, its simple cross-linking, high water absorption, and biocompatibility have facilitated its utility in regulating the interaction with cells or organs. However, three-dimensional (3D) networks of the alginate hydrogel do not provide fibrous anchorage sites such as the collagen fibres in the natural extracellular matrix (ECM). This has partially limited the survival of anchorage-dependent cells in the 3D hydrogel environment. In this report, we established a hybrid hydrogel containing fibrous particles (FP) that closely mimics the ECM. The RGD peptide-coupled FP (R-FP) has a wide range of distribution and was homogeneously dispersed in the hydrogel. The encapsulated human mesenchymal stem cells in the hydrogel could bind to the R-FP presenting remarkable spreading morphology, augmented viability and differentiation. These findings may elicit the significance of a physical interaction in which the R-FP provides structural and biological cues to the cells. This strategy can be widely applicable to a variety of hydrogel systems.

Synergistic effect of dual-functionalized fibrous scaffold with BCP and RGD containing peptide for improved osteogenic differentiation.

Over the last decade, bone tissue engineering scaffolds have been advanced owing to the bioceramic incorporation and biomimetic modification. In this report, a dual-functional fibrous scaffold with a bioceramic and biomolecule is developed, and a combined effect of a dual-modification is investigated. Biphasic calcium phosphate (BCP) is incorporated in electrospun poly (L-lactide) scaffolds, and Arg-Gly-Asp (RGD) peptide is then conjugated through the graft polymerization of acrylic acid by γ-ray irradiation. The scaffolds exhibit the intrinsic properties of BCP as well as RGD peptide, and only RGD peptide improves an adhesion and proliferation of the human mesenchymal stem cell. However, alkaline phosphatase activity and calcium formation are synergistically improved by the BCP and RGD peptide indicating that a favorable microenvironment is constructed for bone formation. Therefore, this combination strategy with bioceramic and biomolecule can be a useful tool for the bone tissue engineering.

Identification of novel non-metal haloperoxidases from the marine metagenome.

Haloperoxidase (HPO, E.C.1.11.1.7) is a metal-containing enzyme oxidizing halonium species, which can be used in the synthesis of halogenated organic compounds, for instance in the production of antimicrobial agents, cosmetics, etc., in the presence of halides and H2O2. To isolate and evaluate a novel non-metal HPO using a culture-independent method, a cassette PCR library was constructed from marine seawater in Japan. We first isolated a novel HPO gene from Pseudomonas putida ATCC11172 by PCR for constructing the chimeric HPO library (HPO11172). HPO11172 showed each single open-reading frame of 828 base pairs coding for 276 amino acids, respectively, and showed 87% similarity with P. putida IF-3 sequences. Approximately 600 transformants screened for chimeric genes between P. putida ATCC11173 and HPO central fragments were able to identify 113 active clones. Among them, we finally isolated 20 novel HPO genes. Sequence analyses of the obtained 20 clones showed higher homology genes with P. putida or Sinorhizobium or Streptomyces strains. Although the HPO A9 clone showed the lowest homology with HPO11172, clones in group B, including CS19, showed a relatively higher homology of 80%, with 70% identy. E. coli cells expressing these HPO chimeric genes were able to successfully bioconvert chlorodimedone with KBr or KCl as substrate.

Hyaluronic acid/chondroitin sulfate-based hydrogel prepared by gamma irradiation technique.

Gamma-ray irradiation of novel hydrogels was used to develop a biocompatible hydrogel system for skin tissue engineering. These novel hydrogels are composed of natural polymers including hyaluronic acid (HA) and chondroitin sulfate (CS), and the synthetic polymer, poly(vinyl alcohol) (PVA). The γ-ray irradiation method has advantages, such as relatively simple manipulation without need of any extra reagents for polymerization and cross-linking. We synthesized HA and CS derivatives with polymerizable residues. The HA/CS/PVA hydrogels with various compositions were prepared by using γ-ray irradiation technique and their physicochemical properties were investigated to evaluate the feasibility of their use as artificial skin substitutes. HA/CS/PVA hydrogels showed an 85-88% degree of gelation under 15 kGy radiation. All HA/CS/PVA hydrogels exhibited more than 90% water content and reached an equilibrium swelling state within 24h. Hydrogels with higher concentrations of hyaluronidase solution and HA/CS content had proportionally higher enzymatic degradation rates. The drug release behaviors from HA/CS/PVA hydrogels were influenced by the composition of the hydrogel and drug properties. Exposure of human keratinocyte (HaCaT) culture to the extracts of HA/CS/PVA hydrogels did not significantly affect the cell viability. All HaCaT cell cultures exposed to the extracts of HA/CS/PVA hydrogels exhibited greater than 92% cell viability. The HaCaT growth in HA/CS/PVA hydrogels gradually increased as a function of culture time. After 7 days, the HaCaT cells in all HA/CA/PVA hydrogels exhibited more than 80% viability compared to the control group HaCaT culture on a culture plate.

Characterization and antimicrobial property of poly(acrylic acid) nanogel containing silver particle prepared by electron beam.

In this study, we developed a one step process to synthesize nanogel containing silver nanoparticles involving electron beam irradiation. Water-soluble silver nitrate powder is dissolved in the distilled water and then poly(acrylic acid) (PAAc) and hexane are put into this silver nitrate solution. These samples are irradiated by an electron beam to make the PAAc nanogels containing silver nanoparticles (Ag/PAAc nanogels). The nanoparticles were characterized by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). In addition, the particle size and zeta-potential were confirmed by a particle size analyzer (PSA). The antibacterial properties of the nanogels were evaluated by paper diffusion test. The Ag/PAAc nanogels had an antibacterial effect against Escherichia coli and Staphylococcus aureus. The nanogels also demonstrated a good healing effect against diabetic ulcer. The size of the Ag/PAAc nanogels decreased with increasing irradiation doses, and the absolute value of the zeta potential increased with increasing irradiation doses. Also, the Ag/PAAc nanogels exhibited good antibacterial activity against both Gram-negative and Gram-positive bacteria. In in vivo wound healing, the Ag/PAAc nanogels have a good healing effect.

Topical treatment of the buccal mucosa and wounded skin in rats with a triamcinolone acetonide-loaded hydrogel prepared using an electron beam.

In this study, a triamcinolone acetonide-loaded hydrogel was prepared by electron beam irradiation and evaluated for use as a buccal mucoadhesive drug delivery system. A poloxamer was modified to have vinyl end groups for preparation of the hydrogel via an irradiation cross-linking reaction. Carbopol was introduced to improve the mucoadhesive properties of the hydrogel. The in vitro release of triamcinolone acetonide from the hydrogel was examined at 37 °C. To investigate the topical therapeutic effect of triamcinolone acetonide on wounded rat skin and buccal mucosa, the appearance and histological changes were evaluated for 15 days after treatment with saline, triamcinolone acetonide solution, triamcinolone acetonide hydrogel, and blank hydrogel, respectively. Triamcinolone acetonide was released constantly from the gel formulation at 37 °C and reach 100% at about 48 h. After 15 days, in the skin of the group treated with the triamcinolone acetonide-loaded hydrogel, the wound was almost completely free of crust and a number of skin appendages, including hair follicles, had formed at the margins of the tissue. Moreover, the inflammatory response in the buccal mucosa was milder than that in the other groups, and the wound surface was completely covered with regenerating, hyperkeratotic, thickened epithelial cells. Our results indicate that the triamcinolone-acetonide hydrogel showed sustained drug release behavior, while causing no significant histopathological changes in buccal and skin tissues. Therefore, this hydrogel system may be a powerful means of drug delivery for buccal administration with controlled release and no tissue irritation.