In this work, a simple g-C3N4 quantum dots enriched MoO3 nanohybrid was formulated for the synergistic photocatalytic degradation of an industrially active organic pollutant, p-chlorophenol (PCP) and ...a widely prescribed antibiotic, rifampicin (RIF). The nanohybrid was synthesised via a facile ultrasonic assisted hydrothermal method and characterized using various characterization analysis. The efficient Z-scheme charge transfer of the nanohybrid resulted in the elimination of 98% PCP and 89% RIF under visible light with a rate constant of 0.012 and 0.006 min−1 respectively. The photocatalysis was attributed to the formation of both hydroxyl (OH•) and superoxide (O2•-) radicals in the resulting nanohybrid. The intermediates formed in the course of reaction were estimated through gas chromatography-mass spectroscopy/mass spectroscopy (GC-MS/MS) analysis and a suitable degradation pathway was constructed. The structural stability and reusability of the nanohybrid was affirmed through X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis to outweigh the industrial potential of the catalyst, with 85% PCP and 80% RIF removal efficiency after six cycles of degradation. In addition, the mineralization of the pollutants was confirmed by total organic carbon analysis. Further, the toxicity of the drug and the formed intermediates was determined using ecological structure activity relationships (ECOSAR) software. On the whole, this work provides an excellent insight for the development of environment-friendly materials in a large scale for the degradation of water-based pollutants.
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•A novel g-C3N4 QDs incorporated MoO3 catalyst was successfully fabricated.•Superior degradation of about 98% p-chlorophenol and 89% rifampicin was achieved in 330 min.•Led to the mitigation of charge carriers and improved visible light activity.•Porous nature of g-C3N4 QDs facilitated more surface-active sites for efficient adsorption.•Exhibition of Z-scheme mechanism with both .•OH and •O2− radicals responsible for photocatalysis.
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Rifampicin is a first-line, highly effective drug currently used orally as a part of a lengthy multi-drug regimen against tuberculosis (TB). Despite the potential of inhaled therapy ...as an effective approach for TB treatment, an inhalable formulation of rifampicin has not yet been developed for clinical use. In order to do so, it is necessary to evaluate its solid-state properties, which regulate important characteristics like solubility, dissolution, aerosolization, stability and bioavailability. In this study, a crystallization technique and spray drying were used to prepare inhalable rifampicin formulations. Spray drying yielded amorphous formulation of rifampicin while crystalline dihydrate and pentahydrate formulations were obtained by crystallization. The powders were evaluated for their solid-state properties, in vitro aerosolization and aerosolization stability for three months when stored at different relative humidity conditions. All formulations had a mean particle size smaller than 3.8 µm and had a fine particle fraction (FPF) higher than 58.0%. Amorphous and crystalline dihydrate formulations showed no change in aerosolization parameters (emitted dose and FPF) upon storage for three months. The amorphous and pentahydrate formulations were found to undergo oxidative degradation upon storage, and a decrease in their drug content was observed. Among the formulations prepared, rifampicin dihydrate formulation showed the least degradation over the three months period. The inhalable rifampicin formulations prepared in this study, being excipient free, have the potential to be delivered as inhaled dry powder high-dose rifampicin to the lungs for effective treatment of TB.
•Electrochemical oxidation of rifampicin and its reaction mechanism.•Study on reaction of rifampicin-quinone with anti-tuberculosis drugs.•Study on poor bioavailability of rifampicin.•Study on ...Pourbaix diagrams of rifampicin.•Study on hydrolysis and decomposition kinetic of rifampicin.
Electrochemical behavior of rifampicin (RIF) as an anti-tuberculosis drug was studied in detail in water/ethanol mixture using different voltammetric techniques. The results indicate that rifampicin is oxidized in two steps, the first step is related to the reversible oxidation of hydroquinone moiety to benzoquinone and the second one is related to the irreversible oxidation of phenolic ring of RIF. In this work, the adsorption activity and diffusion coefficient of RIF was also determined and shows that the first oxidation step is diffusion control while second one is a diffusion/adsorption control process. Furthermore, our results show that the oxidation of RIF (especially in the first step) is complex and highly pH-dependent. The Pourbaix diagram was drawn for this drug and useful information was obtained regarding the oxidized and reduced forms of RIF and the acid/base properties of the species obtained from RIF and its oxidized form (RIF-Q). The first line of tuberculosis drug treatment currently includes the simultaneous use of rifampicin, isoniazid, pyrazinamide and ethambutol (Fixed Dose Combinations, FDCs). Understanding the mechanism of drug-drug interactions is not only useful in preventing drug toxicity or side effects, but also in devising safer treatments for diseases. In this study, based on the obtained electrochemical data, we suggest plausible mechanisms for the reaction of RIF-Q with the medicines prescribed in FDC. The obtained results show that the mentioned drugs through their free amino group can react with RIF-Q. Our findings also show that the rate of these reactions is low in acidic environments such as the stomach and high in neutral or alkaline environments such as the small intestine. In these reactions, ethambutol has the highest rate and pyrazinamide has the lowest rate for the reaction with RIF.
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To enhance the oral bioavailability of rifampicin (RMP), the newly emerging phospholipid complexation technique was employed. Rifampicin–phospholipid complex (RMP-PC) was prepared by ...solvent-evaporation method. Infrared spectroscopy (IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and hot stage microscopy (HSM) analysis were employed to confirm the formation of phospholipid complex. The results reveal hydrogen bond formation and electrostatic interaction between RMP and phospholipid molecule play an important role in the formation of RMP-PC without the formation of a new compound. In comparison with the physical mixture and RMP, solubility studies indicated an enhancement in the aqueous solubility of RMP-PC. Stability studies of RMP-PC in presence of isoniazid showed a remarkable improvement of the stability of the phospholipid complex in comparison to free RMP. Oral bioavailability of RMP-PC was evaluated in Sprague-Dawley (SD) rats and plasma rifampicin estimated by LCMS. RMP-PC exhibited higher peak plasma concentration (54.3 vs. 48.5μg/mL), increased AUC0–∞ (472.4 vs. 147.71 5.812±0.49μgh/mL), increased T1/2 (8.3 vs. 1.5h) when compared to free RMP implying improved bioavailability of the drug. This enhancement can be attributed to the improvement of the aqueous solubility of rifampicin–phospholipid complex. Hence, phospholipid complexation holds a promising potential for increasing oral bioavailability of poorly water soluble drugs.
In this study, we focused on fabrication of porous ultra-thin ZnO nanosheet (PUNs)/CuCo2S4 quantum dots (CCS QDs) for visible light-driven photodegradation of rifampicin (RIF) and Cr(VI) reduction. ...The morphology, structural, optical and textural properties of fabricated photocatalyst were critically analyzed with different analytical and spectroscopic techniques. An exceptionally high RIF degradation (99.97%) and maximum hexavalent Cr(VI) reduction (96.17%) under visible light was achieved at 10 wt% CCS QDs loaded ZnO, which is 213% and 517% greater than bare ZnO PUNs. This enhancement attributed to the improved visible light absorption, interfacial synergistic effect, and high surface-rich active sites. Extremely high generation of ●OH attributed to the spin-orbit coupling in ZnO PUNs@CCS QDs and the existence of oxygen vacancies. Besides, the ZnOPUNs@CCS QDs, forming Z-scheme heterojunctions, enhanced the separation of photogenerated charge carriers. We investigated the influencing factors such as pH, inorganic ions, catalyst dosage and drug dosage on the degradation process. More impressively, a stable performance of ZnO PUNs@CCS QDs obtained even after six consecutive degradation (85.9%) and Cr(VI) reduction (67.7%) cycles. Furthermore, the toxicity of intermediates produced during the photodegradation process were assessed using ECOSAR program. This work provides a new strategy for ZnO-based photocatalysis as a promising candidate for the treatment of various contaminants present in water bodies.
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•ZnO nanosheet coupled CuCo2S4 QDs fabricated via low-temperature reflux method.•Singly ionized oxygen vacancies in ZnO were induced with CuCo2S4 QDs deposition.•Achieved high RIF degradation (99.97%) and Cr(VI) reduction (96.17%).•RIF photodegradation mechanism over CCS QDs@ZnO was proposed.•Reusability and structural stability of the CCS QDs@ZnO were investigated.
Water contamination is regarded as one of the most important concerns in the last decade and its crucial to develop an efficient and productive technique to remediate organic pollutants from waters. ...Photocatalytic degradation processesare advanced oxidation procedure and a promising technique for the degradation of organic pollutants. In this study, we fabricated Ag2S/Zn3V2O8 nanocomposite (AS/ZVO NCs) for the degradation of rifampicin (RIF) by ultrasonicated co-precipitation strategy. The NCs was optimally synthesized with varying deposition concentrations, among which 5%-Ag2S/Zn3V2O8 (5%-AS/ZVO) exhibited superior photocatalytic activity (95.5%) under visible light irradiation. Moreover, the experiments were conducted at diverse operational parameters such as different NCs dosage, different concentration of RIF, pH, and ions, to investigate the impact on the photocatalytic degradation of RIF. Notably, XRD and XPS results of used 5%-AS/ZVO NCs demonstrated commendable stability and possess sustained integrity in structure after six consecutive cycle tests. The scavenging study and radical trapping experiments confirmed the formation of •OH and O2•- during photocatalytic reaction. The mechanism of photocatalytic degradation of RIF by 5%-AS/ZVO NCs was proposed and the pathway was predicted based on the GC-MS results. The current study provides a comprehensive understanding for designing efficient photocatalysts for the environmental remediation applications.
•Ag2S/Zn3V2O8 was prepared for effective photodegradation of rifampicin.••OH and O2•- were primarily involved in photocatalytic reactions.•NCs exhibited excellent photocatalytic stability and structural integrity.•Investigation of intermediate product using GC-MS•The toxicity of intermediate product assessed using ECOSAR program.
Constant exposure to light is prevalent in modern society where light noise, shift work, and jet lag is common. Constant light exposure disrupts circadian rhythm, induces stress and thus influences ...memory performance. We subjected adult male Wistar rats to a two-month exposure to constant light (LL), constant dark or normal light-dark cycles. Significant cognitive impairment and oxidative stress were observed in LL rats without a significant elevation in soluble Aβ1–42 levels. Next, we examined whether long-term exposure to constant light may accelerate dementia in a sub-pathological Aβ model of rats. Normal control rats received ACSF, AD rats received 440 pmol, and sub-pathological Aβ rats (Aβ(s)) received 220 pmol of human Aβ42 peptide in a single unilateral ICV administration. Sub-pathological Aβ rats exposed to constant light (LL + Aβ(s)) show significant memory deficits and oxidative damage, although not significantly different from LL rats. Additionally, constant light promoted aggregation of exogenous Aβ42 in LL + Aβ(s) rats shown by the presence of congophilic plaques. Furthermore, chronic fluoxetine treatment (5 mg/kg/day) rescued rats from the behavioral deficits, oxidative damage and amyloid aggregation. Whereas, rifampicin treatment (20 mg/kg/day) did not reverse the behavioral deficits or oxidative stress but rescued rats from amyloid plaque formation. It was concluded that constant light for two months induces behavioral deficits, oxidative stress, and accelerates aggregation of sub-pathological concentrations of human-Aβ42 peptides in Wistar rats, which is reversed by daily fluoxetine administration.
•Long term light induces behavioural deficits and oxidative damage, but not amyloid dyshomeostasis in Wistar rats.•Long term light exposure promotes aggregation of sub-pathological Aβ42 in rats.•Fluoxetine rescues sub-pathological Aβ42 rats in LL conditions from behavioural deficits and oxidative damage.•Fluoxetine and rifampicin treatments rescue sub-pathological Aβ42 rats in LL conditions from Aβ42 aggregation.
Rifampicin (RIF) plays a pivotal role in the treatment of tuberculosis due to its bactericidal effects. Because the action of RIF is on rpoB gene encoding RNA polymerase β subunit, 95% of RIF ...resistant mutations are present in rpoB gene. The majority of the mutations in rpoB gene are found within an 81bp RIF-resistance determining region (RRDR).
Literatures on RIF resistant mutations published between 2010 and 2016 were thoroughly reviewed.
The most commonly mutated codons in RRDR of rpoB gene are 531, 526 and 516. The possibilities of absence of mutation in RRDR of rpoB gene in MDR-TB isolates in few studies was due to existence of other rare rpoB mutations outside RRDR or different mechanism of rifampicin resistance.
Molecular methods which can identify extensive mutations associated with multiple anti-tuberculous drugs are in urgent need so that the research on drug resistant mutations should be extended.
Objective: Rifampicin and isoniazid are the main tuberculosis treatment regimens requiring blood level measurement to optimize the treatment process. This study aims to analyze rifampicin and ...isoniazid quantitatively in volumetric absorptive microsampling (VAMS) prepared from a small volume of TB patients using HPLC. Methods: Analytes on the VAMS tip were extracted using 1000 ml of acetonitrile containing 10 µg/ml of cilostazol as an internal standard. Analytical separation was performed on the C-18 column at 40 ℃ with a mobile phase mixture of 50 mmol ammonium acetate buffer pH 5.0-acetonitrile-methanol (40:30:30), flow rate 0.5 ml/min. The analysis was carried out with the calibration curve over a range of 1.0–30 µg/ml for rifampicin and 0.4-20 µg/ml for isoniazid. Results: Analyte analysis in 21 patients showed that the measured value of rifampicin was 3.39–16.77 µg/ml, and isoniazid was 2.63–10.43 µg/ml at 2 h post-dose. 52.38% of patients had low blood concentrations in at least one of the drugs, 28.57% of the patients were in the therapeutic range, and 23.81% had a high blood concentration of isoniazid alone. Conclusion: The concentration of rifampicin and isoniazid in 21 tuberculosis patients varied. Dose adjustment is needed because most patients had low blood concentrations of one of the drugs, and a limited number had a high blood isoniazid concentration alone. Only some patients simultaneously had plasma concentrations within the target range of the drugs. This method was valid and reliably utilized for therapeutic drug monitoring of antituberculosis.
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