A 90-Day Tenofovir Reservoir Intravaginal Ring for Mucosal HIV Prophylaxis

A vaginal gel containing the antiretroviral tenofovir (TFV) recently demonstrated 39% protection against HIV infection in women. We designed and evaluated a novel reservoir TFV intravaginal ring (IVR) to potentially improve product effectiveness by providing a more controlled and sustained vaginal dose to maintain cervicovaginal concentrations. Polyurethane tubing of various hydrophilicities was filled with a high-density TFV/glycerol/water semisolid paste and then end-sealed to create IVRs. In vitro, TFV release increased with polyurethane hydrophilicity, with 35 weight percent water-swelling polyurethane IVRs achieving an approximately 10-mg/day release for 90 days with mechanical stiffness similar to that of the commercially available NuvaRing. This design was evaluated in two 90-day in vivo sheep studies for TFV pharmacokinetics and safety. Overall, TFV vaginal tissue, vaginal fluid, and plasma levels were relatively time independent over the 90-day duration at approximately 10⁴ ng/g, 10⁶ ng/g, and 10¹ ng/ml, respectively, near or exceeding the highest observed concentrations in a TFV 1% gel control group. TFV vaginal fluid concentrations were approximately 1,000-fold greater than levels shown to provide significant protection in women using the TFV 1% gel. There were no toxicological findings following placebo and TFV IVR treatment for 28 or 90 days, although slight to moderate increases in inflammatory infiltrates in the vaginal epithelia were observed in these animals compared to naïve animals. In summary, the controlled release of TFV from this reservoir IVR provided elevated sheep vaginal concentrations for 90 days to merit its further evaluation as an HIV prophylactic.     

Simultaneous delivery of tenofovir and acyclovir via an intravaginal ring

Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection "pod IVR" platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ± 335 μg day(-1) (ACV) and 321 ± 207 μg day(-1) (TFV); sheep, 174 ± 14 μg day(-1) (ACV) and 185 ± 34 μg day(-1) (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ± 7.31 μg ml(-1) (ACV) and 20.6 ± 16.2 μg ml(-1) (TFV); cervicovaginal lavage fluid, 118 ± 113 ng ml(-1) (ACV) and 191 ± 125 ng ml(-1) (TFV); tissue, 173 ng g(-1) (ACV) and 93 ng g(-1) (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens.     

Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure Prophylaxis

Intravaginal rings releasing tenofovir (TFV) or its prodrug, tenofovir disoproxil fumarate (TDF), are being evaluated for HIV and herpes simplex virus (HSV) prevention. The current studies were designed to determine the mechanisms of drug accumulation in human vaginal and immune cells. The exposure of vaginal epithelial or T cells to equimolar concentrations of radiolabeled TDF resulted in over 10-fold higher intracellular drug levels than exposure to TFV. Permeability studies demonstrated that TDF, but not TFV, entered cells by passive diffusion. TDF uptake was energy independent but its accumulation followed nonlinear kinetics, and excess unlabeled TDF inhibited radiolabeled TDF uptake in competition studies. The carboxylesterase inhibitor bis-nitrophenyl phosphate reduced TDF uptake, suggesting saturability of intracellular carboxylesterases. In contrast, although TFV uptake was energy dependent, no competition between unlabeled and radiolabeled TFV was observed, and the previously identified transporters, organic anion transporters (OATs) 1 and 3, were not expressed in human vaginal or T cells. The intracellular accumulation of TFV was reduced by the addition of endocytosis inhibitors, and this resulted in the loss of TFV antiviral activity. Kinetics of drug transport and metabolism were monitored by quantifying the parent drugs and their metabolites by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Results were consistent with the identified mechanisms of transport, and the exposure of vaginal epithelial cells to equimolar concentrations of TDF compared to TFV resulted in ∼40-fold higher levels of the active metabolite, tenofovir diphosphate. Together, these findings indicate that substantially lower concentrations of TDF than TFV are needed to protect cells from HIV and HSV-2.     

Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d'Ivoire, in the ANRS 12109 TEmAA Study, Step 2

The aim was to evaluate emtricitabine (FTC) and tenofovir (TFV) neonatal ingestion through breast milk. Median TFV and FTC breast milk doses represented 0.03% and 2%, respectively, of the proposed oral infant doses. Neonatal simulated plasma concentrations were extremely low for TFV but between the half-maximal inhibitory concentration and the adult minimal expected concentration for FTC. The rare children who will acquire HIV despite TDF-FTC therapy will need to be monitored for viral resistance acquisition.     

Impact of Hydroxychloroquine-Loaded Polyurethane Intravaginal Rings on Lactobacilli

The use of polymeric devices for controlled sustained delivery of drugs is a promising approach for the prevention of HIV-1 infection. Unfortunately, certain microbicides, when topically applied vaginally, may be cytotoxic to vaginal epithelial cells and the protective microflora present within the female genital tract. In this study, we evaluated the impact of hydroxychloroquine (HCQ)-loaded, reservoir-type, polyurethane intravaginal rings (IVRs) on the growth of Lactobacillus crispatus and Lactobacillus jensenii and on the viability of vaginal and ectocervical epithelial cells. The IVRs were fabricated using hot-melt injection molding and were capable of providing controlled release of HCQ for 24 days, with mean daily release rates of 17.01 ± 3.6 μg/ml in sodium acetate buffer (pH 4) and 29.45 ± 4.84 μg/ml in MRS broth (pH 6.2). Drug-free IVRs and the released HCQ had no significant effects on bacterial growth or the viability of vaginal or ectocervical epithelial cells. Furthermore, there was no significant impact on the integrity of vaginal epithelial cell monolayers, in comparison with controls, as measured by transepithelial electrical resistance. Overall, this is the first study to evaluate the effects of HCQ-loaded IVRs on the growth of vaginal flora and the integrity of vaginal epithelial cell monolayers.     

Evaluation of Single and Combination Therapies with Tenofovir Disoproxil Fumarate and Emtricitabine In Vitro and in a Robust Mouse Model Supporting High Levels of Hepatitis B Virus Replication

Next-generation therapies for chronic hepatitis B virus (HBV) infection will involve combinations of established and/or experimental drugs. The current study investigated the in vitro and in vivo efficacy of tenofovir disoproxil fumarate (TDF) and/or emtricitabine [(−)-FTC] alone and in combination therapy for HBV infection utilizing the HepAD38 system (human hepatoblastoma cells transfected with HBV). Cellular pharmacology studies demonstrated increased levels of (−)-FTC triphosphate with coincubation of increasing concentrations of TDF, while (−)-FTC had no effect on intracellular tenofovir (TFV) diphosphate levels. Quantification of extracellular HBV by real-time PCR from hepatocytes demonstrated the anti-HBV activity with TDF, (−)-FTC, and their combination. Combination of (−)-FTC with TDF or TFV (ratio, 1:1) had a weighted average combination index of 0.7 for both combination sets, indicating synergistic antiviral effects. No cytotoxic effects were observed with any regimens. Using an in vivo murine model which develops robust HBV viremia in nude mice subcutaneously injected with HepAD38 cells, TDF (33 to 300 mg/kg of body weight/day) suppressed virus replication for up to 10 days posttreatment. At 300 mg/kg/day, (−)-FTC strongly suppressed virus titers to up to 14 days posttreatment. Combination therapy (33 mg/kg/day each drug) sustained suppression of virus titer/ml serum (<1 log₁₀ unit from pretreatment levels) at 14 days posttreatment, while single-drug treatments yielded virus titers 1.5 to 2 log units above the initial virus titers. There was no difference in mean alanine aminotransferase values or mean wet tumor weights for any of the groups, suggesting a lack of drug toxicity. TDF–(−)-FTC combination therapy provides more effective HBV suppression than therapy with each drug alone.     

Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their infants

Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV) transmission in a macaque model, is available as the oral agent tenofovir disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants. Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600 mg FTC at labor onset or prior to a cesarean section. Infants received no drug or a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3 mg/kg as soon as possible after birth. All regimens were safe and well tolerated. Maternal areas under the serum concentration-time curve (AUC) and concentrations at the end of sampling after 24 h (C(24)) were similar between the two doses of TDF; the maximum concentrations of the drugs in serum (C(max)) and cord blood concentrations were higher in women delivering via cesarean section than in those who delivered vaginally (P = 0.04 and 0.046, respectively). The median ratio of the TFV concentration in cord blood to that in the maternal plasma at delivery was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median TFV concentration of 12 ng/ml 12 h after birth. Following administration of a single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their infants, 600 mg of TDF is acceptable as a single dose during labor. Low concentrations at birth support infant dosing as soon after birth as possible. Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of TDF will be necessary to maintain concentrations that are effective for viral suppression.     

Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109)

Thirty-eight human immunodeficiency virus-1 (HIV-1)-infected pregnant women were administered tenofovir disoproxil fumarate (TDF; 300 mg)-emtricitabine (FTC; 200 mg) tablets: two at labor initiation and one daily for 7 days postpartum. Maternal, umbilical, and neonatal plasma tenofovir concentrations were measured by high-performance liquid chromatography and analyzed using a population approach. Data were described using a two-compartment model for the mother, an effect compartment linked to maternal circulation for cord, and a neonatal compartment disconnected after delivery. Absorption was greater for women delivering by caesarian section than for those delivering vaginally. The maternal 600 mg TDF administration before delivery produces the same concentrations as 300 mg administration in other adults. If the time elapsed between maternal administration and delivery is >or=12 h, two tablets of TDF-FTC should be readministered. Tenofovir showed good placental transfer (60%). Administering 13 mg/kg of TDF as soon as possible after birth should produce neonatal concentrations comparable with those observed in adults.     

Plasma and intracellular tenofovir pharmacokinetics in the neonate (ANRS 12109 trial, step 2)

The objective of this study was to investigate for the first time tenofovir (TFV) pharmacokinetics in plasma and peripheral blood mononuclear cells (PBMCs) of the neonate. HIV-1-infected pregnant women received two tablets of tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) at onset of labor and then one tablet daily for 7 days postpartum. A single dose of 13 mg/kg of body weight of TDF was administered to 36 neonates within 12 h of life after the HIV-1-infected mothers had been administered two tablets of TDF-emtricitabine at delivery. A total of 626 samples collected within the 2 days after the drug administration were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and analyzed by a population approach. In the neonate, the median TFV plasma area under the curve and minimal and maximal concentrations, respectively, were 3.73 mg/liter · h and 0.076 and 0.29 mg/liter. In PBMCs, TFV concentrations were detectable in all fetuses, whereas tenofovir diphosphate (TFV-DP) was quantifiable in only two fetuses, suggesting a lag in appearance of TFV-DP. The median TFV-DP neonatal concentration was 146 fmol/10⁶ cells (interquartile range [IQR], 53 to 430 fmol/10⁶ cells); two neonates had very high TFV-DP concentrations (1,530 and 2963 fmol/10⁶ cells). The 13-mg/kg TDF dose given to neonates produced plasma TFV and intracellular active TFV-DP concentrations similar to those in adults. This dose should be given immediately after birth to reduce the delay before the active compound TFV-DP appears in cells.     

Enhanced sorption of the UV filter 4-methylbenzylidene camphor on aged PET microplastics from both experimental and theoretical perspectives

In this study, the morphology and sorption behavior of polyethylene terephthalate (PET) microplastics during the aging process are investigated. To clarify the sorption mechanism of aged PET microplastics, the common sunblock 4-methylbenzylidene camphor (4-MBC) was chosen as the target contaminant, and UV irradiation was used for the laboratory aging simulation. The results show that oxygen-containing functional groups (carboxylic, carbonyl, ketone and hydroxyl groups) increase on the surface of aged PET microplastics. Based on density functional theory (DFT) simulations, the camphor part of 4-MBC acts as a hydrogen bond acceptor, whereas the carboxylic group on aged PET microplastics acts as a hydrogen bond donor. The formation of hydrogen bonding causes increased sorption of 4-MBC on aged PET microplastics. The sorption capacity increased from 5 to 11 μg g⁻¹ for 50 ppb 4-MBC with 100 mg PET microplastics after a five-day aging process. Other environmental factors that affect sorption were also identified; a higher pH value and the presence of salinity reduced the amount of sorption. The sorption of virgin PET ranged from 8.0 to 3.4 μg g⁻¹ and the sorption of aged PET ranged from 22 to 5 μg g⁻¹ at pH 4 to 10. In the presence of salinity (10% seawater), the virgin PET sorption dropped to 2.1 μg g⁻¹ while the aged PET sorption dropped to 4 μg g⁻¹. A similar phenomenon was also observed in the sorption behavior under natural sunlight (the sorption of PET increased from 0.4 to 0.8 μg g⁻¹ after 6 months of aging). The potential risk to ecosystems of aged PET microplastics under prolonged sunlight exposure in the natural environment could be greater than that predicted for virgin microplastics.

The enhanced sorption behavior of aged polyethylene terephthalate (PET) microplastics with 4-methylbenzylidene-camphor (4MBC) via hydrogen bonding is investigated through both experimental and theoretical methods.     

Vaginally Delivered Tenofovir Disoproxil Fumarate Provides Greater Protection than Tenofovir against Genital Herpes in a Murine Model of Efficacy and Safety

Increased susceptibility to genital herpes in medroxyprogesterone-treated mice may provide a surrogate of increased HIV risk and a preclinical biomarker of topical preexposure prophylaxis safety. We evaluated tenofovir disoproxil fumarate (TDF) in this murine model because an intravaginal ring eluting this drug is being advanced into clinical trials. To avoid the complications of surgically inserting a ring, hydroxyethylcellulose (HEC)-stable formulations of TDF were prepared. One week of twice-daily 0.3% TDF gel was well tolerated and did not result in any increase in HSV-2 susceptibility but protected mice from herpes simplex virus 2 (HSV-2) disease compared to mice treated with the HEC placebo gel. No significant increase in inflammatory cytokines or chemokines in vaginal washes or change in cytokine, chemokine, or mitochondrial gene expression in RNA extracted from genital tract tissue was detected. To further evaluate efficacy, mice were treated with gel once daily beginning 12 h prior to high-dose HSV-2 challenge or 2 h before and after viral challenge (BAT24 dosing). The 0.3% TDF gel provided significant protection compared to the HEC gel following either daily (in 9/10 versus 1/10 mice, P < 0.01) or BAT24 (in 14/20 versus 4/20 mice, P < 0.01) dosing. In contrast, 1% tenofovir (TFV) gel protected only 4/10 mice treated with either regimen. Significant protection was also observed with daily 0.03% TDF compared to HEC. Protection was associated with greater murine cellular permeability of radiolabeled TDF than of TFV. Together, these findings suggest that TDF is safe, may provide substantially greater protection against HSV than TFV, and support the further clinical development of a TDF ring.     

Concentrations of tenofovir and emtricitabine in saliva: implications for preexposure prophylaxis of oral HIV acquisition

To prevent acquisition of HIV through oral sex, drugs used for preexposure prophylaxis (Prep) need to diffuse in saliva. We measured tenofovir (TFV) and emtricitabine (FTC) concentrations simultaneously in the plasma and saliva of 41 HIV-infected patients under stable antiretroviral treatment. Mean ratios of saliva/plasma concentration were 3% (±4%) and 86.9% (±124%) for TFV and FTC, respectively. Tenofovir disoproxil fumarate (TDF) should be used in combination with FTC to prevent oral acquisition of HIV.     

Effect of glucose oxidase and pentosanase on the prebiotic potentials of wheat arabinoxylans in an in vitro fermentation system

Arabinoxylans (AXs) treated with enzymes, pentosanase (Pn) and glucose oxidase (GOX) not only offer a promising way to improve wheat product quality but also change their prebiotic potentials by modifying the structures of AXs. In the present study, the different crosslinking degrees of water-extracted arabinoxylans (WEAXs) treated with GOX alone or in combination with Pn + GOX were examined. The structural features and candidate prebiotic capabilities were investigated. It was demonstrated that WEAXs treated with 50 μg g⁻¹ (w/w, enzyme/WEAX) GOX and 200 μg g⁻¹ (w/w, enzyme/WEAX) Pn + 400 μg g⁻¹ (w/w, enzyme/WEAX) GOX exhibited weak gel formation, while WEAXs treated with 400 μg g⁻¹ (w/w, enzyme/WEAX) GOX and 25 μg g⁻¹ (w/w, enzyme/WEAX) Pn + 400 μg g⁻¹ (w/w, enzyme/WEAX) GOX formed strong gels. The ferulic acid content was significantly decreased due to the formation of ferulic acid crosslinking in the enzyme-treated WEAXs (p < 0.05). During in vitro fermentation, GOX and Pn + GOX treatments resulted in significantly (p < 0.05) increased amounts of bifidobacteria compared to WEAX alone. Pn + GOX-treated WEAXs had higher (p < 0.05) bifidobacteria populations than WEAXs treated with GOX alone. The bifidobacteria numbers and the SCFAs content of the weak gels were significantly higher than those in the strong gels under the same enzyme action (p < 0.05). These findings suggested that the increased bifidobacteria populations of GOX-treated WEAXs were due to the formation of ferulic acid crosslinking in contrast to a combination of ferulic acid crosslinking and degradation of the xylan backbone as seen in WEAXs treated with Pn + GOX. The reason the weak gels had better prebiotic potential than the corresponding strong gels was their high content of ferulic acid crosslinking.

GOX and Pn + GOX modification increased the prebiotic potential of WEAX. Pn + GOX treated WEAXs had higher prebiotic potentials than WEAXs treated with GOX. The prebiotic potential of the weak gel was higher than that in the strong gel.     

Synthesis of alginate–polycation capsules of different composition: characterization and their adsorption for [As(iii)] and [As(v)] from aqueous solutions

The uptake of arsenite [As(iii)] and arsenate [As(v)] by functionalized calcium alginate (Ca-Alg) beads from aqueous solutions was investigated. Ca-Alg beads were protonated with poly-l-lysine (PLL) or polyethyleneimine (PEI) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) or glutaraldehyde (GA) as crosslinking agents. Four types of protonated beads were prepared: Ca-Alg-EDC/NHS (PLL or PEI) and Ca-Alg-GA (PLL or PEI). Fourier transform infrared spectroscopy in total attenuated reflection mode (FTIR-ATR), analysis showed presence and increased intensity of bands corresponding to OH, NH, CH₂ and CH₃ groups in modifications with both polycations. In addition, thermogravimetric analysis and atomic force microscopy of all modified capsules showed an increase in thermal stability and uniformity of the capsules, respectively. Ca-Alg-EDC/NHS-PLL beads had the maximum adsorption capacity of [As(v)] (312.9 ± 4.7 μg g⁻¹ of the alginate) at pH 7.0 and 15 minute exposure, while Ca-Alg-EDC/NHS-PEI beads had the maximum adsorption capacity of [As(iii)] (1052.1 ± 4.6 μg g⁻¹ of alginate). However, all these EDC containing beads were degraded in the presence of citrate. Ca-Alg-GA-PEI beads removed 252.8 ± 9.7 μg of [As(v)] μg g⁻¹ of alginate and 524.7 ± 5.3 de [As(iii)] μg g⁻¹ of alginate, resulting the most stable capsules and suitable for As removal.

A simple protonation of alginate beads allows the absorption of arsenate and arsenite.     

Intracellular time course, pharmacokinetics, and biodistribution of isoniazid and rifabutin following pulmonary delivery of inhalable microparticles to mice

Intracellular concentrations of isoniazid and rifabutin resulting from administration of inhalable microparticles of these drugs to phorbol-differentiated THP-1 cells and the pharmacokinetics and biodistribution of these drugs upon inhalation of microparticles or intravenous administration of free drugs to mice were investigated. In cultured cells, both microparticles and dissolved drugs established peak concentrations of isoniazid (~1.4 and 1.1 μg/10⁶ cells) and rifabutin (~2 μg/ml and ~1.4 μg/10⁶ cells) within 10 min. Microparticles maintained the intracellular concentration of isoniazid for 24 h and rifabutin for 96 h, whereas dissolved drugs did not. The following pharmacokinetic parameters were calculated using WinNonlin from samples obtained after inhalation using an in-house apparatus (figures in parentheses refer to parameters obtained after intravenous administration of an equivalent amount, i.e., 100 μg of either drug, to parallel groups): isoniazid, serum half-life (t_1/2) = 18.63 ± 5.89 h (3.91 ± 1.06 h), maximum concentration in serum (C_max) = 2.37 ± 0.23 μg·ml⁻¹ (3.24 ± 0.57 μg·ml⁻¹), area under the concentration-time curve from 0 to 24 h (AUC_0-24) = 55.34 ± 13.72 μg/ml⁻¹ h⁻¹ (16.64 ± 1.80 μg/ml⁻¹ h⁻¹), and clearance (CL) = 63.90 ± 13.32 ml·h⁻¹ (4.43 ± 1.85 ml·h⁻¹); rifabutin, t_1/2 = 119.49 ± 29.62 h (20.18 ± 4.02 h), C_max = 1.59 ± 0.01 μg·ml⁻¹ (3.47 ± 0.33 μg·ml⁻¹), AUC_0-96 = 109.35 ± 14.78 μg/ml⁻¹ h⁻¹ (90.82 ± 7.46 μg/ml⁻¹ h⁻¹), and CL = 11.68 ± 7.00 ml·h⁻¹ (1.03 ± 0.11 ml·h⁻¹). Drug targeting to the lungs in general and alveolar macrophages in particular was observed. It was concluded that inhaled microparticles can reduce dose frequency and improve the pharmacologic index of the drug combination.     

Synthesis and antibacterial and antiviral activities of myricetin derivatives containing a 1,2,4-triazole Schiff base

A series of novel myricetin derivatives containing a 1,2,4-triazole Schiff base were designed and synthesized. Their structures were systematically characterized using ¹H NMR, ¹³C NMR, and HRMS. During antibacterial bioassays, 6f, 6i, and 6q demonstrated a good inhibitory effect against Xanthomonas axonopodis pv. citri (Xac), with half-maximal effective concentration (EC₅₀) values of 10.0, 9.4, and 8.8 μg mL⁻¹, respectively, which were better than those of bismerthiazol (54.9 μg mL⁻¹) and thiodiazole copper (61.1 μg mL⁻¹). Note that 6w demonstrated a good inhibitory effect against Ralstonia solanacearum (Rs) with and EC₅₀ value of 15.5 μg mL⁻¹, which was better than those of bismerthiazol (55.2 μg mL⁻¹) and thiodiazole copper (127.9 μg mL⁻¹). Similarly, 6a, 6d, and 6e demonstrated a good inhibitory effect against Xanthomonas oryzae pv. oryzae (Xoo) with EC₅₀ values of 47.1, 61.2, and 61.0 μg mL⁻¹, respectively, which were better than those of bismerthiazol (148.2 μg mL⁻¹) and thiodiazole copper (175.5 μg mL⁻¹). Furthermore, we used scanning electron microscopy (SEM) to study the possible sterilization process of the target compound 6q against Xac. The results indicated the possibility of destroying the bacterial cell membrane structure, resulting in an incomplete bacterial structure, and thus achieving inhibition. Furthermore, antiviral bioassays revealed that most compounds exhibited excellent antiviral activity against tobacco mosaic virus (TMV) at a concentration of 500 μg mL⁻¹. The results of the molecular docking studies for 6g with TMV-CP (PDB code: 1EI7) showed that compound 6g had partially interacted with TMV-CP. Therefore, mechanistic studies of the action of compound 6g could be further studied based on that.

The myricetin derivatives containing a 1,2,4-triazole Schiff base were designed and synthesized. Antibacterial mechanism was investigated through SEM.     

Retraction: One pot green preparation of Seabuckthorn silver nanoparticles (SBT@AgNPs) featuring high stability and longevity,antibacterial, antioxidant potential: a nano disinfectant future perspective

Retraction of ‘One pot green preparation of Seabuckthorn silver nanoparticles (SBT@AgNPs) featuring high stability and longevity, antibacterial, antioxidant potential: a nano disinfectant future perspective’ by Thiyagarajan Kalaiyarasan et al., RSC Adv., 2017, 7, 51130–51141, https://doi.org/10.1039/C7RA10262C.

I, the undersigned author, hereby wholly retract this RSC Advances article due to the following instances of matched/similar images that have been identified that weaken this article, which occurred due to honest human errors.Following the previous publication of a correction to correct errors in Fig. 1, 3, 7 and 9, further instances of duplicating images have been identified within the corrected Fig. 3 and 7, as well as additional errors in the original article, that undermine this article.In Fig. 3 of the correction notice:The panel for freshly prepared S. enterica MTCC-3219 2 μg ml⁻¹ 10⁻¹⁰ is identical to the panel for S. typhirmurium MTCC-3224 4 μg ml⁻¹ 10⁻⁵ after one year of storage, to the panel 1 h treated with SBT@AgNPs in Fig. 7, and to the panels E. coli MTCC No. 62 6 μg ml⁻¹ and 8 μg ml⁻¹ in Fig. 5 of ref. 1.The panel for freshly prepared S. typhirmurium MTCC-3224 6 μg ml⁻¹ 10⁻¹⁰ is identical to the panel for S. typhirmurium MTCC-3224 6 μg ml⁻¹ 10⁻¹⁰ after one year of storage and to the panel 0.5 h treated with SBT@AgNPs in Fig. 7.The panel for freshly prepared S. typhirmurium MTCC-3224 4 μg ml⁻¹ 10⁻⁵ is identical to the panel for freshly prepared S. enterica MTCC-3219 6 μg ml⁻¹ 10⁻¹⁰.The panel for freshly prepared S. typhirmurium MTCC-3224 2 μg ml⁻¹ 10⁻¹⁰ is identical to the panel for S. typhirmurium MTCC-3224 6 μg ml⁻¹ 10⁻⁵ after one year of storage.The panel for freshly prepared S. typhirmurium MTCC-3224 4 μg ml⁻¹ 10⁻¹⁰ is identical to the panel for S. typhirmurium MTCC-3224 2 μg ml⁻¹ 10⁻¹⁰ after one year of storage.The panel for S. enterica MTCC-3219 4 μg ml⁻¹ 10⁻⁵ after one year of storage is identical to the panel for S. enterica MTCC-3219 6 μg ml⁻¹ 10⁻¹⁰ after one year of storage.In Fig. 3a, a′, c and c′ of the original article, the error bars are erroneous.In Fig. 4 of the original article, both the panels for S. typhirmurium are identical.Thiyagarajan Kalaiyarasan and Vijay K. Bharti responded to all enquiries and submitted data related to the above concerns. However, to avoid any future ambiguity to the readers, the article is retracted.Vijay K. Bharti and O. P. Chaurasia were informed about the retraction of the article but have not responded.Signed: Kalaiyarasan ThiyagarajanDate: 1/6/2022Retraction endorsed by Laura Fisher, Executive Editor, RSC Advances