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Nermin E Eleraky,1 Mahmoud El-Badry,1 Mahmoud M Omar,2,3 Wesam M El-Koussi,4 Noha G Mohamed,5 Mohamed A Abdel-Lateef,6 Abeer S Hassan7 1Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Deraya University, Minia, Egypt; 3Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt; 4Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Sohag University, Sohag, Egypt; 5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sphinx University, Assiut, Egypt; 6Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt; 7Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, EgyptCorrespondence: Nermin E Eleraky, Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt, Tel +20 1014017239, Fax +20 (088-002) 2345631, Email Nermineleraky@pharm.aun.edu.egPurpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs.Methods: Transferosomes were developed by using 33 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits.Results: The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of − 11.23 ± 2.5 mV, and PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration.Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies.Graphical Abstract: Keywords: transferosomes, curcumin, in situ gels, coronavirus 2, SARS-CoV-2, intranasal delivery

People frequently administer Tizanidine (TIZ) to treat spasticity resulting from diseases like multiple sclerosis or spinal cord injuries. It also helps prevent muscle spasms. It helps to relax and release tense and stiff muscles by inhibiting specific nerve signals in the brain and spinal cord. The technique employed in this study made use of the unique ability of benzofurazan to confer fluorescent character when reacted with TIZ at specific conditions. This fluorogenic property was harnessed to evolve a remarkably sensitive, affordable, and selective method to quantify TIZ. The resulting yellow fluorescent product was observedat a wavelength beam of 532.9 nm, and an excitation wavelength beam of 474.9 nm was applied. By looking at the response across the TIZ concentration, the calibration chart's linearity was assessed in the range of 40-500 ng/mL. By computation, the approach's detection level (LOD) was determined to be 11.9 ng/mL, while the quantitation level was approximated to be 36 ng/mL. All pertinent factors impacting the strategy's efficacy were thoroughly inspected and adjusted accordingly. The proposed strategy was validated following the guidelines outlined by the ICH. The outcomes confirmed the method's capability for the accurate quantifying of TIZ in tablets, spiked plasma, and pharmaceutical assessing content uniformity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Recently, nanomaterials have attracted a lot of attention due to their potential as effective fluorescent nano-sensor probes. They were distinguishing substitutes for other luminescent techniques, such as fluorescent dyes and luminous derivatization, because of their affordability, environmental friendliness, and special photocatalytic properties. In the suggested work, a straightforward method was used to create boron and nitrogen carbon dots (B@CDs) with a good quantum yield value of 31.15 % utilizing boric acid and di-sodium EDTA. For the purpose of characterizing QDs, a variety of instruments were employed, such as transmission electron microscopy, fluorescence spectroscopy, X-ray FTIR, and UV-VIS spectroscopy. Nebivolol (NEB) is a cardiovascular medication used globally to treat congestive heart failure and hypertension, is in the meantime. For this reason, a brand-new, environmentally friendly analytical technique was created to determine the amount of human plasma, uniformity test, and commercial nebivolol (NEB) tablets. After gradually adding NEB, the response of B@CQDs was enhanced at 438 nm (excitation at 371 nm). The calibration graph ranged between 20 and 500 ng mL -1 with a quantification limit (LOQ) of 2.50 ng mL -1 and a detection limit (LOD) of 0.82 ng mL -1 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aspartame is an artificial sweetener used in drinks and many foods. International Agency for Research on Cancer classified aspartame as possibly carcinogenic to humans (IARC Group 2B). In this study, a sensitive and selective spectrofluorimetric method was developed to detect aspartame. The method is based on switching on the fluorescence activity of aspartame upon its condensation with O-phthalaldehyde (Roth's reaction) in the presence of 2-mercaptoethanol. The reaction product was detected fluorometrically at λ em of 438 nm after λ ex of 340 nm. All reaction conditions required to yield the optimal fluorescence intensity were observed and investigated. Furthermore, the approach was validated according to ICH guidelines. Upon plotting the concentrations of aspartame against their associated fluorescence intensity values, the relationship between the two variables was linear within the range of 0.5-3.0 μg/mL. Furthermore, the method was employed to analyze the quantity of aspartame in commercial packages and soft drinks with an acceptable level of recovery. In addition, the Green Solvents Selecting Tool, Complementary Green Analytical Procedure Index, and the Analytical Greenness Metric tool were used to evaluate the sustainability and the greenness of the developed methodology., (© 2024 John Wiley & Sons Ltd.)

Indigo carmine (IN-CR) is a synthetic blue dye widely used as a coloring agent in various food and beverage products. It is recognized for its ability to enhance the visual appeal, hue, and consistency of food products. However, recent studies have raised concerns about the potential health risks associated with this substance. Therefore, a highly sensitive analytical tool is required for the trace determination of IN-CR in food products. This study describes the spectral characteristics of micellar-enhanced fluorescence of europium (III)-doxycycline complex and its employment as a sensor for the development of a highly sensitive fluorimetric assay for the trace determination of IN-CR. The complex was formed in an alkaline medium containing hydrogen peroxide and encapsulated into cetyltrimethylammonium bromide micelles. This micellar-encapsulated complex exhibited significantly enhanced fluorescence at a wavelength of 613.5 nm, overlapping with the maximum absorption peak of IN-CR at 610 nm. This inner-filter effect phenomenon resulted in IN-CR's concentration-dependent quenching of the complex's fluorescence. The fluorescence quenching of the complex by inner-filter effect of IN-CR was adopted in the development of a highly sensitive fluorimetric assay for IN-CR. The conditions of the assay were refined, and the optimum procedures were established. The assay was validated for its performance characteristics, and all the validation criteria were met. The assay displayed linearity within the IN-CR concentration range of 100-1250 ng mL -1 , with a limit of detection at 41.2 ng mL -1 . Importantly, the assay exhibited no interference from other substances commonly used as food additives. The recoveries ranged from 99.11 % to 101.57 %, with relative standard deviations ranging from 1.34 % to 1.89 %.The assay was successfully applied to the determination of IN-CR in commercial syrup products, and the recoveries ranged from 93.5 % to 106.32 % with relative standard deviations ≤4.72 %, confirming the reliability of the assay. The proposed assay provides some key advantages, including a novel application of the europium (III)-doxycycline complex as a fluorescence sensor for the determination of IN-CR in real syrups innovative, high sensitivity and selectivity, simplicity of analysis procedures, time-saving of entire analysis protocol. In conclusion, the assay serves as a valuable tool for quantifying IN-CR in food products, facilitating the assessment of both food quality and safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A newly green method for the sensitive quantification of cloperastine, a cough suppressant, in spiked human plasma and its pharmaceutical formulation was designed for the first time. The established method depends on the enhancement of the weak fluorescence of cloperastine using 50 mM sulfuric acid to impair the photoinduced electron transfer produced from the nitrogen atom of piperidine moiety in cloperastine. This full protonation in an acid medium leads to an enhancement in the fluorescence of cloperastine, permitting its linear determination from 0.2 to 5.0 µg/mL with LOD and LOQ of 0.04 and 0.13 µg/mL, respectively. Moreover, the studied drug was estimated in its pharmaceutical market formulations as well as spiked human plasma. Furthermore, the greenness of the described method was evaluated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The development of sustainable analytical methodologies that minimize hazards, waste generation, and energy consumption has become crucial. This study introduces pioneering green‒blue-white approaches for the simultaneous quantification of montelukast sodium (MLK) and fexofenadine hydrochloride (FEX) in combination formulations. The first approach employs an ultra-performance liquid chromatographic method (UPLC) with a green micellar mobile phase of 0.02 M sodium dodecyl sulfate and 10% 1-pentanol (65:35%). The method demonstrated excellent resolution, peak symmetry, and a short analysis time, with retention times of 3.53 min for MLK and 1.67 min for FEX. The MLK and FEX linearities were 1-260 and 1.2-312 μg/mL, respectively. The second approach involves complementary built-in spectroscopic techniques (second derivative, third derivative, and ratio difference methods) using water as a solvent, providing a green, simple, low-cost alternative in laboratories where expensive chromatographic devices may not be readily available. The MLK and FEX linearities were 3-50 and 3-60 μg/mL, respectively. All methods were comprehensively validated and showed satisfactory results. The proposed methods demonstrated excellent linearity (r 2  ≥ 0.9990), accuracy (recovery 98.5-101.5%), and precision (RSD ≤ 2%) across wide concentration ranges. A multifaceted evaluation was conducted to assess the environmental sustainability, real-world applicability, and economic viability of the proposed methods in comparison with previously reported techniques. This comprehensive assessment leveraged several state-of-the-art tools, including NEMI, ComplexGAPI, AGREE, ESA, BAGI, and RGB12. The suggested approaches exhibited favorable quadrant profiles in the NEMI and ComplexGAPI assessments, coupled with higher AGREE scores (0.90, 0.86) than reported (0.62, 0.74, 0.75, 0.69, 0.74, 0.74, and 0.75), in addition to higher ESA score (88, 92) than reported (75, 84, 85, 79, 82, 82, and 83), collectively affirming their environmentally friendly credentials. Moreover, we embraced the innovative notions of 'blueness' and 'whiteness' assessment by harnessing the recently formulated BAGI and RGB12 algorithms. The higher BAGI score (90, 82.5) than reported (72.5, 70, 70, 67.5, 67.5, 67.5, and 72.5), confirmed the excellent real-world applicability of the proposed methods, while the notable RGB12 indices (89.8, 88.1) than reported (67.8, 72.8, 71.5, 67.1, 73.7, 70.3, and 73.2), validated their cost-effectiveness and overall sustainability, contributing to an eco-friendly future for quality control processes., (© 2024. The Author(s).)

Indigo carmine dye is one of the most widely used dyes in various fields. In this study, the ethanolic extract of red dragon fruit peel (Ex-RDFP) was employed as a green fluorescence probe for measuring the synthetic dye indigo carmine. At a fluorescence excitation of 290.5 nm, the Ex-RDFP exhibits a fluorescence emission band at 341.5 nm. Meanwhile, the indigo carmine dye possesses an absorption spectrum at a maximum peak of 290 nm. Consequently, the fluorescence intensity of the Ex-RDFP was reduced upon the addition of indigo carmine solution due to the inner filter effect mechanism. This quenching in the fluorescence intensity of Ex-RDFP was substantially associated with the indigo carmine concentration at a linear scale of 1.0-7.0 μg mL -1 ( r 2 = 0.9993). Furthermore, the limit of detection and the limit of quantitation of the method were found to be 0.209 μg mL -1 and 0.635 μg mL -1 , respectively. The optimal analytical conditions, such as solvent used for dilution, pH, reaction time, volume of the reagent, and temperature, were examined and carefully studied. In addition, the proposed method was successfully applied to detect indigo carmine dye in various natural syrup samples, including lemon syrup, apple syrup, cantaloupe syrup, pineapple syrup, and guava syrup, with acceptable recovery values. The method's beneficial sustainability footprint was found by using an extensive greenness analysis that incorporated the modified National Environmental Methods Index (NEMI), the complex Green Analytical Procedure Index (GAPI), and the Analytical Greenness Calculator (AGREE) prep algorithms. In addition, "whiteness" and "blueness" were also assessed with the newly released (Red Green Blue 12) RGB12 and Blue Applicability Grade Index (BAGI) computational methods, emphasizing the benefit of the proposed method in terms of analytical efficiency, sustainability, and economy. The suggested technique is the answer to the worldwide popularity of ecologically conscious solutions by providing a green-and-white substitute for traditional techniques and advancing towards creating more sustainable quality control procedures in the future., Competing Interests: There is no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)

The diagnosis of prostate cancer has been evolving in the current decade, with expected mortality rates of 499,000 death by the year 2030. Apalutamide (APL) has been approved in 2018 as the first drug for the controlling of prostate cancer. APL significant success warrantied its high global sales, which are expected to surpass 58% of segment market sales (together with another drug; enzalutamide). Therefore, new, fast and environmentally friendly analytical methods are required for its determination for the quality control and biological monitoring purposes. The proposed research designs and evaluates the first fluorimetric approach based on novel porous green boron-doped carbon quantum dots (B@CDs) for the determination of APL in biopharmaceutical matrices. The synthetic approach has high quantum yield (31.15%). B@CDs were characterized using several tools, including transmission electron microscopy (TEM), dynamic light scattering (DLS), FTIR and Energy dispersive X-ray spectroscopy (EDX) which proved their improved surface properties with an average nano-diameter of 3.0 nm. The interaction between B@CDs and APL led to enhancement their fluorescence at 441 nm (excitation at 372 nm). The approach was validated for the determination of APL within concentration range of 15.0-700.0 ng mL - 1 with quantification limit LOQ 4.37 ng mL - 1 and detection limit LOD 1.44 ng mL - 1 . The approach was successfully applied for the determination of APL in human plasma and pharmaceutical monitoring of its marketed tablet form. Then, the approach was assessed for its environmental impact using different metrics and proved its ecological greenness., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Atopic dermatitis (AD) is a persistent, inflammatory skin condition that impacts approximately 15 to 20% of children and 1 to 3% of adults globally. Common skin manifestations include papules, papulovesicular, and brown or red patches with swelling, crusting, and flaking. Therefore, the drug abrocitinib (ABR) was approved by the US FDA as an oral treatment for atopic dermatitis. The present study outlines the development of innovative, thermostable, and pH-stable organic solvent-free nitrogen-doped carbon dots (N@CQDs) synthesized through a one-step method for evaluating ABR with a notable quantum yield of 33.84% to minimize the use of organic solvents. Their cost-effectiveness, eco-friendly characteristics, and outstanding photocatalytic properties have established them as a promising alternative to conventional luminescent techniques like fluorescent dyes and luminous derivatization technique. The reaction of ABR with N@CQDs led to a significant decrease in the luminescent response of the produced green and stable carbon quantum dots at 513 nm. The detection range was determined to be 1.0-150.0 ng mL -1 , with a lower limit of quantitation (LOQ) equal to 0.52 ng mL -1 based on the linear graph. The green method effectively used for analysis of ABR in pharmaceutical tablets and pharmacokinetic study with high sensitivity., (© 2024 John Wiley & Sons Ltd.)

In this study, a phenothiazine-thiosemicarbazide (PTZDS) probe was synthesized and characterized. The synthesized PTZDS probe exhibited a yellow color, with a native fluorescence emission at λ emission = 550 nm and λ excitation = 450 nm. Over other metal ions, the probe exhibited significant selectivity and sensitivity towards Hg 2+ and Cu 2+ . The probe showed fluorescence quenching along with a minor shift in the absorbance spectra from 400 to 450 nm and 430 nm in the presence of Hg 2+ and Cu 2+ , respectively. In addition, the color of the synthesized probe remarkedly faded with the addition of Hg 2+ or Cu 2+ . Fluorescence measurements, infrared spectroscopy (IR), and density functional theory studies were employed to elucidate the binding process in the PTZDS + Cu 2+ and PTZDS + Hg 2+ sensor systems. Furthermore, photophysical investigations of the synthesized probe with Hg 2+ and Cu 2+ were performed. Finally, the probe was successfully employed as a solid-state thin layer chromatography (TLC) optical sensor for detecting Hg 2+ and Cu 2+ ions., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Background: Sexual and gender-based violence (SGBV) is a prevalent issue in sub-Saharan Africa (SSA), causing injuries and trauma with severe consequences for survivors. This scoping review aimed to explore the range of research evidence on injuries and trauma resulting from SGBV among survivors in SSA and identify research gaps., Methods: The review employed the Arksey and O'Malley methodological framework, conducting extensive literature searches across multiple electronic databases using keywords, Boolean operators, medical subject heading terms and manual searches of reference lists. It included studies focusing on injuries and trauma from SGBV, regardless of gender or age, published between 2012 and 2023, and involved an SSA countries. Two authors independently screened articles, performed data extraction and quality appraisal, with discrepancies resolved through discussions or a third author. Descriptive analysis and narrative synthesis were used to report the findings., Results: After screening 569 potentially eligible articles, 20 studies were included for data extraction and analysis. Of the 20 included studies, most were cross-sectional studies (n = 15; 75%) from South Africa (n = 11; 55%), and involved women (n = 15; 75%). The included studies reported significant burden of injuries and trauma resulting from SGBV, affecting various populations, including sexually abused children, married women, visually impaired women, refugees, and female students. Factors associated with injuries and trauma included the duration of abuse, severity of injuries sustained, marital status, family dynamics, and timing of incidents. SGBV had a significant impact on mental health, leading to post-traumatic stress disorder, depression, anxiety, suicidal ideations, and psychological trauma. Survivors faced challenges in accessing healthcare and support services, particularly in rural areas, with traditional healers sometimes providing the only mental health care available. Disparities were observed between urban and rural areas in the prevalence and patterns of SGBV, with rural women experiencing more repeated sexual assaults and non-genital injuries., Conclusion: This scoping review highlights the need for targeted interventions to address SGBV and its consequences, improve access to healthcare and support services, and enhance mental health support for survivors. Further research is required to fill existing gaps and develop evidence-based strategies to mitigate the impact of SGBV on survivors in SSA., (© 2024. The Author(s).)

In this work, two validated approaches were used for estimating hydroxyzine HCl for the first time using resonance Rayleigh scattering (RRS) and spectrofluorimetric techniques. The suggested approaches relied on forming an association complex between hydroxyzine HCl and 2,4,5,7-tetraiodofluorescein (erythrosin B) reagent in an acidic media. The quenching in the fluorescence intensity of 2,4,5,7-tetraiodofluorescein by hydroxyzine at 551.5 nm (excitation = 527.5 nm) was used for determining the studied drug by the spectrofluorimetric technique. The RRS approach is based on amplifying the RRS spectrum at 348 nm upon the interaction of hydroxyzine HCl with 2,4,5,7-tetraiodofluorescein. The spectrofluorimetric methodology and the RRS methodology produced linear results within ranges of 0.15-1.5 μg ml -1 and 0.1-1.2 μg ml -1 , respectively. LOD values for these methods were determined to be 0.047 μg ml -1 and 0.033 μg ml -1 , respectively. The content of hydroxyzine HCl in its pharmaceutical tablet was estimated using the developed procedures with acceptable recoveries. Additionally, the application of four greenness and whiteness algorithms shows that they are superior to the previously reported method in terms of sustainability, economics, analytical performance, and practicality., (© 2024 John Wiley & Sons Ltd.)

This study introduces a practical and cost-effective method for tracking diltiazem (DLZ) analytically. It utilizes a fluorimetric approach that relies on the modulation of fluorescence intensity of a dye called erythrosine B. Through a one-pot experiment performed in an acidic environment, a complex is rapidly formed between DLZ and erythrosine B. By observing the decrease in erythrosine B emission, a linear calibration plot is established, enabling the detection and quantification of DLZ concentrations ranging from 40 to 850 ng/ml. The estimated limits of detection and quantitation were 10.5 and 32.1 ng/ml, respectively. The variables affecting the DLZ-dye complex system were carefully adjusted. The validity of the approach was confirmed through a thorough evaluation based on the criteria set by ICH guidelines. The accuracy and precision of the methodology were evaluated, and the standard deviation and relative standard deviation were below 2. The strategy was successfully employed to analyze DLZ in tablets and capsules, and no significant variation between the proposed and reported methods as the values of the estimated t-test and F-test at five determinations were below 2.306 and 6.338, respectively. Notably, the method adheres to the principle of green chemistry by utilizing distilled water as the dispersing medium., (© 2024 John Wiley & Sons Ltd.)

For the first time, clemastine was estimated in this work utilizing two validated resonance Rayleigh scattering (RRS) and fluorimetric methods. The methods relied on forming an association complex in an acidic medium between eosin Y reagent and clemastine. In the spectrofluorimetric approach, the investigated drug was quantified by quenching the fluorescence-emission intensity of eosin Y at 543.5 nm. The RRS method relied on enhancing the RRS spectrum at 331.8 nm, which is produced when eosin Y interacts with clemastine. Suitable conditions were established for the reaction to achieve maximum sensitivity. The linear values obtained from the spectrofluorimetric approach and the RRS method fall into the ranges of 0.2-1.5 µg mL - 1 and 0.25-2.0 µg mL - 1 , respectively. It was established that the detection limits for these methods were 0.045 µg mL - 1 and 0.059 µg mL - 1 , respectively. The developed methodologies yielded acceptable recoveries when used to estimate the quantity of clemastine in its pharmaceutical tablet dosage form. Regarding the use of greener solvents that were chosen, the suggested and reported methods were compared with the help of the Green Solvents Selecting (GSST) tool for assessing hazardous solvents to achieve sustainability. Furthermore, analytical Eco scale and comprehensive assessments of whiteness, blueness, and greenness were carried out utilizing Modified NEMI, ComplexGAPI, and AGREE evaluation tools. Additionally, recently developed tools such as BAGI and RGB 12 were applied to assess the blueness and the whiteness of the suggested methods., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Daily, the number of women who die around the world reaches an average of 800; these deaths are a result of obstetric complications in pregnancy and childbirth, and 99% of these deaths occur in low- and middle-income countries. This review probes the use of antenatal care (ANC) and skilled birth delivery (SBD) services in sub-Saharan Africa (SSA) and highlights research gaps using Arksey and O'Malley's methodological approach. The screening of abstracts and full text was carried out by two independent authors who ensured the eligibility of data extraction from the included articles. An exploration of the data was undertaken with descriptive analyses. In total, 350 potentially eligible articles were screened, and 137 studies were included for data extraction and analysis. From the 137 included studies, the majority were from Ethiopia ( n = 40, 29.2%), followed by Nigeria ( n = 30, 21.9%). Most of the studies were published between 2019 and 2023 ( n = 84, 61%). Significant trends and challenges with ANC and SBD services emerged from the studies. It is revealed that there are wide gaps in the utilization of ANC and SBD services. Policy attention, intervention strategies to improve access, resources, rural-urban disparity, and women's literacy are recommended to improve the utilization of ANC and SBD services in SSA countries.

In an acidic buffered solution, erythrosine B can react with amiodarone to form an association complex, which not only generates great enhancement in resonance Rayleigh scattering (RRS) spectrum of erythrosine B at 346.5 nm but also results in quenching of fluorescence spectra of erythrosine B at λ emission  = 550.4 nm/λ excitation  = 528.5 nm. In addition, the formed erythrosine B-amiodarone complex produces a new absorbance peak at 555 nm. The spectral characteristics of the RRS, absorbance, and fluorescence spectra, as well as the optimum analytical conditions, were studied and investigated. As a result, new spectroscopic methods were developed to determine amiodarone by utilizing erythrosine B as a probe. Moreover, the ICH guidelines were used to validate the developed RRS, photometric, and fluorimetric methods. The enhancements in the absorbance and the RRS intensity and the decrease in the fluorescence intensity of the used probe were proportional to the concentration of amiodarone in ranges of 2.5-20.0, 0.2-2.5, and 0.25-1.75 μg/mL, respectively. Furthermore, limit of detection values were 0.52 ng/mL for the spectrophotometric method, 0.051 μg/mL for the RRS method, and 0.075 μg/mL for the fluorimetric method. Moreover, with good recoveries, the developed spectroscopic procedures were applied to analyze amiodarone in its commercial tablets., (© 2024 John Wiley & Sons Ltd.)

In this study, netilmicin (NTM) was selectively assessed in its dosage forms after a facile derivatization reaction. The proposed approach was based on the interaction between NTM and o-phthalaldehyde/2-mercaptoethanol (Roth's reagent). The reaction product was fluorometrically measured at λ emission of 434 nm after λ excitation of 338 nm. All reaction conditions for achieving the optimum fluorescence switch-on activity were visualized and monitored. Moreover, the method was validated under ICH guidelines, and was linear over the range 30-210 ng/ml after plotting netilmicin concentrations against the corresponding fluorescence intensity values. In addition, the selectivity of the developed method was investigated against either the co-formulated drug (dexamethasone) or a common ophthalmic drop excipient (benzalkonium chloride) without interference from either of them. Furthermore, the developed method was applied to assay netilmicin in various samples of pharmaceutical eye drops with good recovery. Finally, multicriteria greenness and whiteness metrics were used to evaluate the sustainability, greenness, and whiteness of the approach. The applied tools were the AGREE algorithm, the RGB 12 algorithm, and HEXAGON., (© 2023 John Wiley & Sons Ltd.)

Background: Definite treatment for glioma is not exist, and with increased drug resistance, more effort should be paid to identify new prognostic biomarkers and molecular targets for therapy for glioma patients., Aim: The current study aimed to evaluate the immunohistochemical (IHC) expression of MTAP and A-Kinase Interacting Protein 1 (AKIP1) in astrocytoma and to investigate their association with the clinicopathological characters of these cases., Methods: Totally 66 cases of astrocytoma patients involved in this study. Cases underwent tumor resection and tissue sections were stained with MTAP, AKIP1 and IDH1 by IHC and evaluated in different grades of astrocytoma and their association with survival and response to therapy was investigated., Results: High AKIP1 expression was positively correlated with treatment resistance and progressive disease. Positive IDH and retained MTAP expressions had shown better treatment response rather than negative IDH and lost MTAP. High AKIP, negative IDH and loss of MTAP expressions were significantly associated with poor survival outcome., Conclusion: Irrespective to grade and IDH status, the loss of MTAP immunoreactivity and high AKIP1 expression are predictive factors in astrocytoma, and they may be used as a biomarker for guiding astrocytoma management and prognosis surveillance.

Netilmicin is an aminoglycoside antibiotic used to treat infections caused by a broad spectrum of Gram-negative and Gram-positive bacteria and is pharmaceutically formulated in ophthalmic dosage forms. In this study, two spectrofluorimetric approaches were designed and developed to switch-on the fluorescence activity of NTC. The first method, or Hantzsch (HNZ) method, was relied on measuring the generated fluorescence intensity upon the condensation of NTC with acetylacetone and formaldehyde (Hantzsch reaction) at λ emis =483 nm/λ excit =425.5 nm. While the second fluorometric method (NHD method) was relied on measuring the generated fluorescence intensity upon the condensation of NTC with ninhydrin/phenylacetaldehyde at λ emis =482.2 nm/λ excit =385.8 nm. The reaction conditions for the two approaches were well investigated and optimized. The selectivity study for the methods was investigated by determining NTC in the presence of the co-formulated drug (dexamethasone) and pharmaceutical excipients. The validation for two approaches was performed based on ICH guidelines, and ranges of linearity were 0.1-1.2 and 1.5-6.0 µg/mL, while LOD values were 0.039 and 0.207 µg/mL for the HNZ method and the NHD method, respectively. Finally, NTC has been determined in different ophthalmic preparations by the proposed approaches with adequate recovery values., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Naftidrofuryl is a vasodilator medication used for treating cerebral and peripheral vascular diseases. In this study, two spectroscopical techniques, spectrofluorimetric and resonance Rayleigh scattering (RRS), were utilized to quantify naftidrofuryl in its pharmaceutical samples. The developed methodologies in this study rely on a facile process of forming an association complex between erythrosine B reagent and naftidrofuryl under acidic conditions. The fluorimetric assay is based on the ability of naftidrofuryl to quench and decrease the native fluorescence intensity of the reagent when measured at λ emis . = 550 nm ( λ excit . = 526 nm). Under similar reaction conditions, the RRS method relies on the observed amplification in the RRS spectrum of the reagent at a wavelength of 577 nm following its interaction with naftidrofuryl. The methods exhibited linearity within the ranges 0.2-1.6 μg/ml (r 2  = 0.999) and 0.1-1.4 μg/ml (r 2  = 0.9994), with limit of quantitation values of 0.146 and 0.099 μg/ml, and limit of detection values of 0.048 and 0.032 μg/ml, for the fluorometric and the RRS methods, respectively. Moreover, the quenching between the dye and naftidrofuryl was studied using Stern-Volmer analysis, and the methodologies were experimentally optimized and validated. Additionally, acceptable recoveries were achieved when the procedures were applied to determine naftidrofuryl in pharmaceutical samples., (© 2023 John Wiley & Sons Ltd.)

Background: The World Health Organization recognises injuries as a growing global public health problem. While there are several causes of injuries and trauma, relevant research is mostly centred on road traffic accidents, burns, and drowning with less focus on violence-related injuries/trauma such as sexual and gender-based violence (SGBV). To identify priority research topics, prioritisation, and development of practice guidelines to mitigate the impact of injuries/trauma resulting from SGBV, this systematic scoping review will aim to map and describe the range of research relating to injuries/trauma due to SGBV in the global context., Methods: A scoping review guided by Arksey and O'Malley's methodological framework will be conducted. Literature relating to injuries/trauma and SGBV will be searched in PubMed, SCOPUS, and PsycINFO, CINAHL, Web of Science, Google Scholar, Trip, guideline repositories, websites, and reference list of included articles. This study will include evidence sources focused on the epidemiological burden, guidelines for out-of-hospital and in-hospital care of victims, barriers or facilitators to reporting and obtaining healthcare, and approaches for mitigating injuries/trauma due to SGBV. The search will be limited to publications within 10 years (2012 to 2023). Two authors will apply the eligibility criteria to identify potentially relevant citations. The data will be extracted in duplicate and methodological quality assessed using varied tools (Mixed Method Quality Appraisal Tool; and Appraisal of Guidelines, Research and Evaluation instrument). The study will be reported in keeping with the Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews., Discussion: The scoping review will highlight existing literature on injuries/trauma due to SGBV and identify gaps to facilitate research prioritisation, development of guidelines, and resource allocation to alleviate the impact of injuries/trauma resulting from SGBV. This study's findings will be disseminated via a series of meetings with key stakeholders (local and international) in the field of healthcare, policy, social welfare, GBV interest groups, and others. Also, the final scoping review results will be presented at relevant workshops, meetings, and conferences. Moreover, this study's findings will be disseminated via journal publications and policy briefs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Principles of Green Analytical Chemistry recommended preferring using reagents from renewable sources and eliminating toxic reagents. Vachellia nilotica is a widespread plant throughout different parts of the world. In this study, using microwave energy, fluorescent carbon dots were synthesized for the first time from Vachellia nilotica pods. The morphology of the prepared carbon dots was characterized by SEM and TEM techniques, and the spectroscopic character exhibit green emission at 480 nm at λ ex  = 386.5 nm. This fluorescence can be effectively quenched by adding Fe (III) ions (Method I). Furthermore, Vachellia nilotica pods were extracted by different solvents, including methanol, deionized water, absolute ethanol, acetone, acetonitrile, and DMF. The acetonitrile extract of Vachellia nilotica exhibited a strong red fluorescence emission at 673.9 at λ ex  = 410 nm. Among various types of salt metals, only Fe (III) can effectively quench the fluorescence intensity of the acetonitrile extract (method II). Moreover, the bright yellow color of the aqueous extract can be changed into violet color. The absorbance of the resulted color can be spectrophotometrically measured at λ max  = 530 nm (method III). The best analytical factors were optimized for the developed methods. The developed methods were applied to determine Fe (III) in different water samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A sensitive and selective phenothiazine-based sensor (PTZ) has been successfully synthesized. The sensor PTZ displayed specific identification of CN - 'turn-off' fluorescence responses with a quick reaction and strong reversibility in an acetonitrile:water (90:10, V/V) solution. The sensor PTZ for detecting CN - exhibits the marked advantages of quenching the fluorescence intensity, fast response time (60 s), and low value of the detection limit. The concentration that is authorized for drinking water by the WHO (1.9 μM) is far higher than the detection limit, which was found to be 9.11 × 10 -9 . The sensor displays distinct colorimetric and spectrofluorometric detection for CN - anion due to the addition of CN - anion to the electron-deficient vinyl group of PTZ, which reduces intramolecular charge transfer efficiencies. The 1:2 binding mechanism of PTZ with CN - was validated by fluorescence titration, Job's plot, HRMS, 1 H NMR, FTIR analysis, and density functional theory (DFT) investigations, among other methods. Additionally, the PTZ sensor was successfully used to precisely and accurately detect cyanide anions in actual water samples., (© 2023 John Wiley & Sons Ltd.)

Turmeric, a spice known for its therapeutic benefits, is a major source of curcumin which is a polyphenol with anti-inflammatory properties. It aids in treating arthritis, anxiety, metabolic syndrome, liver disease, hyperlipidemia, and inflammatory diseases. In this study, a novel fluorescence probe was designed to detect the adulteration of curcumin by metanil yellow (a harmful artificial dye). The probe was synthesized from the carbonization and conversion of the Tannic acid-Eu 3+ complex to bright fluorescence Eu-carbon dots in the presence of orthophosphoric acid. The size, morphological, and optical features of the formed Eu-carbon dots were characterized by UV, SEM, TEM, and FTIR techniques. Furthermore, the formed Eu-carbon dots possess unique fluorescence excitation and emission features at 307.5 nm and 340.6 nm, respectively. These fluorescence features can be successfully quenched upon the addition of metanil yellow dye. The value of quenching in the fluorescence intensity of the Eu-C-dots was directly proportional to the dye's concentration. The LOD value for the proposed method was 0.390 µg/mL with a linear range of 1.0-15.0 µg/mL. Furthermore, the methodology exhibited good recovery values for determining the studied dye without any interference from the presence of curcumin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Indigo Carmine is a hazardous dye and produces an allergic action for humans despite the excessive use of the dye in several industrial fields. A sensitive and simple fluorescent assay for determining Indigo Carmine relying on quenching of the fluorescent europium-doped carbon dots by the action of inner filter effect was developed. This sensing platform involved the preparation of europium-doped carbon dots from the hydrothermal carbonization of tannic acid and europium chloride, which was used as fluorescent reagent with a distinctive excitation/emission wavelength at 307/340 nm. Both excitation and emission fluorescence of prepared carbon dots can be successfully quenched by adding Indigo Carmine dye. The developed spectrofluorimetric method exhibits good linearity with the concentration of Indigo Carmine dye in the range of 1.5 to 10.0 μg/ml and provided a limit of detection (LOD) value of 0.40 μg/ml. Furthermore, the prepared carbon nanoparticles were identified and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and ultraviolet (UV)-spectrophotometer techniques. In addition, the developed detecting approach was applied to determine Indigo Carmine in juice samples with acceptable recovery., (© 2022 John Wiley & Sons Ltd.)

Nitazoxanide is an antimicrobial compound that was originally developed as an antiprotozoal drug. Recently nitazoxanide has been identified as broad-spectrum antiviral agent and redirected for the remediation of some respiratory tract viral infections. In this study, the spectrofluorimetric technique has been applied to determine Nitazoxanide (NTX) in tablets or its metabolite, tizoxanide (TZD), in human urine samples. The developed methodology is based on oxidizing NTX (non-fluorescence) into a highly fluorescent product by sodium hypochlorite. The fluorescence emission intensity was measured at 436.5 nm after fluorescence excitation at 362.5 nm. After optimizing all conditions, the analytical procedures and bio-analytical steps were evaluated and validated using ICH and FDA criteria, respectively. The method linearity, LOQ, and LOD values of NTX were 1.0-5.0 µg/mL, 0.434, and 0.143 µg/mL, respectively. The other novelty side of the presented work is the application of cobalt ferrite (CoFe 2 O 4 ) nanoparticles (NPs) as a magnetic solid-phase for the pre-concentration and extraction process. The synthesized magnetic nanoparticles were characterized by scanning electron microscope and zeta sizer techniques. Finally, the utilized magnetic nanoparticles exhibited good recovery results for pre-concentration and extraction of NTX or its metabolite from spiked and real human urine samples, respectively., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Patient-centered care (PCC) approach has continued to gain recognition globally as the key to providing quality healthcare. However, this concept is not fully integrated into the management of primary health care (PHC) in existing nursing practice due to numerous challenges. Among these challenges is the perception of nursing on PCC in the Primary Health Care system. This study seeks to present the results of qualitative research performed at various selected PHC centres on nurses' perceptions in PCC practice. This study aim was to explore the perception of nurses on PCC., Methods: A qualitative action research approach was adopted. The study involved 30 local government PHC centres located in Osun State Southwest of the federal republic of Nigeria. Data was collected through a semi-structured interview guide questions. Thereafter, data analysis was performed using thematic analysis and NVivo 12 software to generate themes, subthemes, and codes., Results: PCC perceptions of nurses that was revealed in our findings were categorised into positive and negative themes. The negative themes include: poor approach by the nurses and lack of enforcement agency. The positive themes that emerged include: outcome driven healthcare, valued care provider, communication to sharpen care and driven healthcare service., Conclusion: There is need for continuous training, and upgrading of nurses in line with global recommended standards of providing quality healthcare service delivery to the people. Therefore, the federal and state governments and local government council through the Nursing and Midwifery Council body should regulate, supervise, monitor and enforce the use and implementation of PCC in the PHC healthcare system., (© 2022. The Author(s).)

Selective fluorometric detection and determination of uranium ions is provided here using a novel fluorescent reagent, namely (E)-4-([4-hydroxynaphthalen-1-yl]diazenyl)-N-(5-methyleisoxazol-3-yl) benzenesulfonamide (U VI reagent). The U VI reagent offers a selective fluorescence enhancement behaviour at emission wavelength = 557 nm. The parameters affecting fluorometric detection of uranium ions, such as the pH, solvent type, ligand concentration, interaction time, and interfering ions, were investigated and adjusted. The proposed U VI reagent can detect and determine uranium ions even at low concentrations, for which the obtained limit of detection was 0.1 ppm. Additionally, this proposed determination protocol was successfully used to detect, monitor, and determine uranium ions in actual water samples., (© 2022 John Wiley & Sons Ltd.)

Polyvinylpyrrolidone stabilized silver nanoparticles (PV-AgNPs) were synthesized from AgNO 3 /trisodium citrate and with the assistance of microwave energy. The synthesized PV-AgNPs were found to own an actual peroxidase mimicking activity. This catalytic activity can oxidize the non-fluorescence reagent (o-phenylenediamine) to a high fluorescence reaction product (2,3-diaminophenazine). The reaction product exhibited a fluorescence emission at 563 nm upon the excitation at 420. Among many metals, only mercury (II) ions can inhibit the catalytic activity of PV-AgNPs nanozyme. Accordingly, the fluorescence intensity of the reaction product has been successfully quenched. This quenching effect in the fluorescence intensity was directly proportional to the concentration of mercury (II). Depending on this finding, a simple, cost-effective, and selective spectrofluorimetric approach has been designed for mercury (II) detection in water samples. The linear relationship between the inhibition in fluorescence intensity and mercury (II) concentration was found in 20-2000 nM with a detection limit of 8.9 nM., (© 2022. The Author(s).)

In this study, a fluorescence azothiazol-benzenesulfonamide derivative (M-sensor) was prepared for the determination of Mg 2+ ions in different samples. The utilized M-sensor exhibited an emission fluorescence activity at 587 nm upon excitation at 537 nm. The developed method was based on the quenching effect of Mg 2+ ions on the fluorescence intensity of the M-sensor with the above-mentioned fluorescence features. Furthermore, the utilized M-sensor was complexed with Mg 2+ ions in the molar ratio of 1:1 (Mg 2+ to M-sensor) and the selectivity of M-sensor toward Mg 2+ against other metals ions, and the reversibility and reusability of the sensor were studied and verified. After optimization of the fluorometric detection, the quenching effect was directly proportional to the increase in the concentration of Mg 2+ in the linear range 100-600 ng ml -1 with a limit of detection value of 18 ng ml -1 . The fluorescence sensor was successfully applied with good recovery for the determination of Mg 2+ in water samples and different pharmaceutical samples (ampoules and suspension) without any interference from aluminium., (© 2022 John Wiley & Sons Ltd.)

In this study, a facile nanoparticle catalytic sensor for resonance Rayleigh scattering quantification of mercury (II) ion was developed. The developed approach is relied on the selective inhibition of the peroxidase-like activity of polyvinylpyrrolidone-stabilized silver nanoparticles (PVP-Ag-NPs) by mercury (II) ions. The synthesized PVP-Ag-NPs oxidize the aqueous solution of O-Phenylenediamine (colorless) to 2,3-phenazinediamine (bright yellow) and their resonance Rayleigh scattering (RRS) activity was completely suppressed. When mercury (II) was introduced, the RRS activity of PVP-Ag-NPs was turned on combined with a reduction of the intensity of the yellow color. The enhancement in the RRS intensity was related to the concentration of mercury (II) in the linear range of 10-2000 nM. The smaller size (4.5 nm), the large surface area and the uniform size (PDI = 0.379) of the synthesized PVP-Ag-NPs offered a higher chance for interaction between mercury (II) and PVP-Ag-NPs with the advantages of high sensitivity (LOD = 4 nM) and excellent selectivity for mercury (II) detection over several metals and anions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

α-Difluoromethylornithine or Eflornithine is an FDA-approved drug used for the treatment of Sleeping Sickness (as vials dosage form) and also used for diminishing the unwanted excess facial hair in the hirsutism (as creams dosage form). The proposed work is based on the condensation interaction between the amino moiety of Eflornithine and O-phthalaldehyde/2-mercaptoethanol to form a highly fluorescent isoindole derivative. The fluorescence and the Resonance Rayleigh Scattering (RRS) intensities of the reaction product were greatly augmented upon the addition of hexadecyl-trimethyl ammonium bromide by 153% and 250%, respectively. After optimization of the reaction conditions, the formed isoindole derivative was measured fluorometrically at λ emission = 429 nm after λ excitation = 337 nm. Moreover, the significant augmentation in the RRS intensity of the formed product was measured at λ max = 422 nm. In regards to accuracy, sensitivity, robustness and precision, the proposed methods were validated according to ICH guidelines. Furthermore, the proposed methods were successfully applied for the assay of Eflornithine in various commercial brands of the pharmaceutical cream samples with good recovery. In addition to the current fluorometric method was confirmed to be effective in the assaying of Eflornithine in spiked plasma and urine specimens with good recovery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, rapid resonance Rayleigh scattering (RRS), spectrophotometric, and spectrofluorimetric methods were performed for facile quantitation of daclatasvir dihydrochloride without interference from sofosbuvir (a co-formulated anti-hepatitis C virus drug). The proposed approaches were based on forming a binary complex between daclatasvir dihydrochloride and merbromin reagent at pH 4.1. The binary complex was measured spectrophotometrically at λ max = 544 nm. The spectrofluorimetric approach relied on the quenching effect of daclatasvir dihydrochloride on the fluorescence strength of merbromin at λ Emission = 545 nm. The RRS approach depended on augmentation in the merbromin RRS spectrum at 363 nm upon addition of daclatasvir dihydrochloride. The presented methodologies were linear over the concentration ranges 2.5-15.0, 0.2-1.6 and 0.15-3.0 μg ml -1 with detection limits of 0.45, 0.046, and 0.036 μg ml -1 for the spectrophotometric approach, the spectrofluorometric approach, and RRS approach, respectively. Current approaches were validated in compliance with International Council for Harmonisation guidelines and utilized practically to estimate daclatasvir dihydrochloride either in binary mixtures with sofosbuvir or in its commercial tablet dosage form with good results. Moreover, the test for content uniformity was applied successfully on commercial tablets using the current spectroscopic approaches., (© 2021 John Wiley & Sons Ltd.)

An innovative thin-layer chromatography method coupled with the fluorescence detection was developed for a specific estimation of ledipasvir. The separation was achieved on plates of silica gel 60 F254 using ethylacetate: hexane: acetonitrile: triethylamine; (6: 3.5: 1.5: 0.5, $\mathrm{v}/\mathrm{v}/\mathrm{v}/\mathrm{v}$) as a mobile phase system. The method involved the exposure of the developed thin-layer chromatography plate of ledipasvir to strong ultraviolet irradiation, resulting in a great enhancement in the fluorescence properties of ledipasvir. The irradiated plates were scanned after the excitation at 315 $\mathrm{nm}$. The method provided a sufficient separation of ledipasvir from sofosbuvir with ${R}_F$values of 0.28 and 0.36 for ledipasvir and sofosbuvir, respectively. The developed procedures were validated based on guidelines from the International Conference on Harmonization and Food and Drug Administration guidelines. The calibration curve was linear over the range of 5-50 $\mathrm{ng}/\mathrm{band}$. The excellent analytical features of the proposed method allow to the specific determination of ledipasvir in pharmaceutical tablets without interference from sofosbuvir or excipients. As the main elimination route for ledipasvir is via the fecal excretion (86%), the method was applied for the estimation of ledipasvir in fecal specimens with adequate recovery. In addition, the proposed method was applied for testing the content uniformity of ledipasvir in the pharmaceutical tablets., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Eflornithine (EFN) is an anti- Trypanosoma brucei agent for the medication of sleeping sickness and widely distributed for the treatment of hirsutism (unwanted facial hair in women). The presented work demonstrates a comprehensive analytical approach for the spectrofluorometric determination of EFN in commercial cream samples and various biological samples. The proposed method is based on the formation of a highly yellow-green fluorescence dihydropyridine derivative after the interaction between EFN and acetylacetone/formaldehyde reagent in a slightly acidic medium. Furthermore, the optimal variables such as reagent volumes, pH of the medium, heating time, buffer volume, heating temperature and diluting solvent were carefully selected to achieve the maximum fluorescence activity. The fluorescence activity for the formed derivative was measured at λ emission = 477 nm after λ excitation = 418 nm. Concerning linearity, accuracy, sensitivity, precision and robustness, the presented method was validated and verified according to ICH guidelines. Moreover, the proposed work offered a selective determination for EFN in various brands of pharmaceutical cream without any interference from excipients. Eventually, the current approach was assured to be successful in the estimation of EFN in urine and plasma samples with acceptable recovery results., (© 2021 The Authors.)

In this study, spectrofluorimetric and resonance Rayleigh scattering techniques were applied for the first time for determination of rupatadine through two validated methods. The proposed methods were based on a facile association complex formation between rupatadine and erythrosin B reagent in acidic medium. Spectrofluorimetric determination relied on the quenching effect of rupatadine on the fluorescence intensity of erythrosin B at 556 nm (excitation = 530 nm). Conversely, the resonance Rayleigh scattering (RRS) method relied on enhancement in the resonance Rayleigh scattering spectrum of erythrosin B at 344 nm after the addition of rupatadine. The developed methods produced linear results over ranges 0.15-2.0 μg/ml and 0.1-1.5 μg/ml, with detection limits of 0.030 μg/ml and 0.018 μg/ml for the spectrofluorimetric method and the RRS method, respectively. All reaction conditions for rupatadine-erythrosin B formation were optimized experimentally and both methods were validated according to International Council for Harmonisation guidelines. The developed methods were applied to estimate rupatadine content in its pharmaceutical tablet dosage form with acceptable recoveries. Furthermore, a content uniformity test for the commercial rupatadine tablets was successfully applied by the suggested spectroscopic methods according to United States Pharmacopeia guidelines., (© 2020 John Wiley & Sons Ltd.)

Terbinafine hydrochloride is a potent antifungal drug indicated for oral and topical treatment of mycoses. A resonance Rayleigh scattering (RRS) method was developed for the determination of terbinafine hydrochloride through a feasible complexation reaction with erythrosine B. In a weakly acidic medium (acetate buffer, pH 5.0), terbinafine hydrochloride can react with erythrosine B through the electrostatic attraction and virtue of hydrophobic force to form an ion-association complex. The reaction resulted in the appearance of a new RRS peak at 369 nm. The RRS peak was increased by increasing the concentration of terbinafine hydrochloride in the linear range of 0.1-1.5 µg ml -1 . All the reaction conditions (erythrosine B concentration, buffer volume, diluting solvent and pH) were optimized. The detection limit was 0.029 µg ml -1 while the quantitation limit was 0.089 µg ml -1 . The suggested method after its validation was successfully applied for the determination of terbinafine hydrochloride in different pharmaceutical formulations (tablets and cream) with sufficient recovery., Competing Interests: There is no conflict of interest to declare., (© 2021 The Authors.)

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in North America, underscoring the need for the development of new therapeutic strategies for the management of this disease. Although many drugs are pre-clinically tested every year, only a few are selected to be evaluated in clinical trials, and only a small number of these are successfully incorporated into standard care. Inaccuracies with the initial in vitro drug testing may be responsible for some of these failures. Drug testing is often performed using 2D monolayer cultures or 3D spheroid models. Here, we investigate the impact that these different in vitro models have on the carboplatin response of four EOC cell lines, and in particular how different 3D models (polydimethylsiloxane-based microfluidic chips and ultra low attachment plates) influence drug sensitivity within the same cell line. Our results show that carboplatin responses were observed in both the 3D spheroid models tested using apoptosis/cell death markers by flow cytometry. Contrary to previously reported observations, these were not associated with a significant decrease in spheroid size. For the majority of the EOC cell lines (3 out of 4) a similar carboplatin response was observed when comparing both spheroid methods. Interestingly, two cell lines classified as resistant to carboplatin in 2D cultures became sensitive in the 3D models, and one sensitive cell line in 2D culture showed resistance in 3D spheroids. Our results highlight the challenges of choosing the appropriate pre-clinical models for drug testing., Competing Interests: The authors have declared that no competing interests exist.

A validated thin-layer chromatography (TLC) method combined with fluorescence detection mode was developed for the selective determination of a recently approved anti-hepatitis C virus (HCV) drug (velpatasvir). The separation was performed on silica gel 60 F 254 plates using ethylacetate:methanol:triethylamine (48:1.5:1.0, v/v/v) as a mobile phase. Plates were scanned in the fluorescence mode after excitation at 335 nm. This method provided an excellent separation of velpatasvir from sofosbuvir with R F values of 0.22 and 0.46 for velpatasvir and sofosbuvir, respectively, after scanning the developed plates in the ultraviolet detection mode at 335 nm. The calibration curve was linear over the range 4-40 ng/band with a correlation coefficient of 0.9994. The developed procedure was validated according to ICH guidelines with a detection limit of 1.30 ng/band and quantitation limit of 3.95 ng/band. The suggested method could selectively determine velpatasvir with high sensitivity in a synthetic tablet powder containing a co-formulated anti-HCV drug (sofosbuvir) without any interference from excipients or sofosbuvir. In addition, the method was successfully applied for determination of velpatasvir in spiked human plasma with adequate % recovery., (© 2020 John Wiley & Sons, Ltd.)

A fast, low-cost, sensitive, and selective spectrofluorimetric method for the determination of ledipasvir was developed and validated. The method is based on an enhancement in the native fluorescence intensity of ledipasvir by 500% of its original value by the formation of hydrogen bonds between the cited drug and Tween-20 in the micellar system (pH = 5.0). All fluorescence measurements were carried out at 425 nm and 340 nm for emission and excitation wavelengths, respectively. A linear relationship between the concentration of ledipasvir and the observed fluorescence intensity was achieved in the range of 0.1-2.0 μg ml -1 with 0.028, 0.084 μg ml -1 , for detection and quantitation limits, respectively. The acquired selectivity and sensitivity using the proposed method facilitate the analysis of ledipasvir in spiked human plasma with sufficient percentage recovery (95.36-99.30%). The proposed method was developed and validated according to International Council for Harmonisation (ICH) guidelines. Moreover, the cited drug was successfully determined in its pharmaceutical dosage form using the proposed method. In addition, the validity of the proposed results was statistically confirmed using Student's t-test, variance ratio F-test, and interval hypothesis test., (© 2019 John Wiley & Sons, Ltd.)

A highly sensitive and specific fluorescence dependent approach was created for quantitation of a recently approved anti-HCV drug (ledipasvir). This approach relies on the innovative enhancement in fluorescence intensity of ledipasvir upon exposing the cited drug to direct UV irradiation as a photo-physical fluorescence enhancer. The fluorescence of the resultant solution was measured at an emission peak of 375 nm (321 nm excitation). The photoluminescence properties of the resultant product were carefully examined and the quantitative rectilinear concentration plot for the method was 5.0-150.0 ng mL -1 with a detection limit of 0.9 ng mL -1 and a quantitation limit of 2.7 ng mL -1 . The excellent analytical features of the proposed method allow to the specific and sensitive estimation of ledipasvir either in plasma samples or in tablet dosage form without any interference from pharmaceutical excipients or other co-formulated anti-HCV drugs (sofosbuvir). The developed analytical and bio-analytical procedures were created and validated according to ICH guidelines and FDA guidelines, respectively. Since the main elimination route for ledipasvir is via faecal excretion, the studied drug was determined for the first time in faecal samples by the method with adequate recovery. Moreover, the pharmacokinetic parameters ( C max , t max , t 1/2 , AUC 0- t , and AUC 0-∞ ) for ledipasvir were determined by the proposed method. Additionally, the proposed method was successfully applied for supervising the content uniformity for ledipasvir in its pharmaceutical tablets., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We investigated the molecular mechanism(s) by which insulin prevents Bcl2-modifying factor (Bmf)-induced renal proximal tubular cell (RPTC) apoptosis and loss in diabetic mice. Transgenic mice (Tg) mice specifically overexpressing human BMF in RPTCs and non-Tg littermates were studied at 10 to 20 weeks of age. Non-diabetic littermates, diabetic Akita mice +/- insulin implant, Akita Tg mice specifically overexpressing heterogeneous nuclear ribonucleoprotein F (hnRNP F) in their RPTCs and immortalized rat renal proximal tubular cells (IRPTCs) were also studied. BMF-Tg mice exhibited higher systolic blood pressure, urinary albumin/creatinine ratio, RPTC apoptosis and urinary RPTCs than non-Tg mice. Insulin treatment in Akita mice and Akita mice overexpressing hnRNP F suppressed Bmf expression and RPTC apoptosis. In hyperinsulinemic-euglycemic wild type mice, renal Bmf expression was down-regulated with up-regulation of hnRNP F. In vitro, insulin inhibited high glucose-stimulation of Bmf expression, predominantly via p44/42 mitogen-activated protein kinase (MAPK) signaling. Transfection of p44/42 MAPK or hnRNP F small interfering RNA (siRNA) prevented insulin inhibition of Bmf expression. HnRNP F inhibited Bmf transcription via hnRNP F-responsive element in the Bmf promoter. Our results demonstrate that hnRNP F suppression of Bmf transcription is an important mechanism by which insulin protects RPTCs from apoptosis in diabetes.

Multicellular tumour spheroids are an ideal in vitro tumour model to study clonal heterogeneity and drug resistance in cancer research because different cell types can be mixed at will. However, measuring the individual response of each cell population over time is challenging: current methods are either destructive, such as flow cytometry, or cannot image throughout a spheroid, such as confocal microscopy. Our group previously developed a wide-field fluorescence hyperspectral imaging system to study spheroids formed and cultured in microfluidic chips. In the present study, two subclones of a single parental ovarian cancer cell line transfected to express different fluorophores were produced and co-culture spheroids were formed on-chip using ratios forming highly asymmetric subpopulations. We performed a 3D proliferation assay on each cell population forming the spheroids that matched the 2D growth behaviour. Response assays to PARP inhibitors and platinum-based drugs were also performed to follow the clonal evolution of mixed populations. Our experiments show that hyperspectral imaging can detect spheroid response before observing a decrease in spheroid diameter. Hyperspectral imaging and microfluidic-based spheroid assays provide a versatile solution to study clonal heterogeneity, able to measure response in subpopulations presenting as little as 10% of the initial spheroid., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is an urgent need and strong clinical and pharmaceutical interest in developing assays that allow for the direct testing of therapeutic agents on primary tissues. Current technologies fail to provide the required sample longevity, throughput, and integration with standard clinically proven assays to make the approach viable. Here we report a microfluidic micro-histological platform that enables ex vivo culture of a large array of prostate and ovarian cancer micro-dissected tissue (MDT) followed by direct on-chip fixation and paraffination, a process we term paraffin-embedding lithography (PEL). The result is a high density MDT-Micro Array (MDTMA) compatible with standard clinical histopathology that can be used to analyse ex vivo tumor response or resistance to therapeutic agents. The cellular morphology and tissue architecture are preserved in MDTs throughout the 15 day culture period. We also demonstrate how this methodology can be used to study molecular pathways involved in cancer by performing in-depth characterization of biological and pharmacological mechanisms such as p65 nuclear translocation via TNF stimuli, and to predict the treatment outcome in the clinic via MDT response to taxane-based therapies.

Daclatasvir dihydrochloride (DAC) is a new, direct-acting antiviral drug with powerful inhibitory effect against all hepatitis C virus (HCV) genotypes. A sensitive, simple, fast and specific fluorometric method for estimation of DAC in the presence of sofosbuvir was developed and validated. The method is based on reinforcement the fluorescence intensity of DAC by 170% of its original value in an aqueous solution of hexadecyl trimethyl ammonium bromide (pH 5.5, Teorell and Stenhagen buffer). The fluorescence intensity measurements were accomplished at 387 nm with 328 nm for excitation wavelength. A linear relationship was achieved between the DAC concentration and the fluorescence intensity in a range of 50.0-2000.0 ng ml -1 with 0.9998 and 0.9999 for the determination and correlation coefficients, respectively. The detection and quantitation limits were 13.4, 40.8 ng ml -1 , respectively. The excellent sensitivity and specificity of the proposed method allowed the efficient estimation of DAC in real human plasma with adequate recovery (81.78 ± 1.57), and the selective determination for DAC in its commercial dosage form without interference from tablet excipient. Moreover, the proposed method was expanded to examine the stability of DAC by determination the parent drug of DAC in the presence of its oxidative, alkaline, acidic, UV, daylight and sunlight degradations products in agreement with ICH guidelines. Furthermore, the kinetic study of acidic and oxidative degradations of DAC was inspected. In addition, the half-life times of the reaction (t 1/2 ) and the first-order reaction rate constants were estimated. Moreover, a suggestion for the degradation pathway was supposed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Velpatasvir (VLP) is a new, oral, direct-acting antiviral with potent inhibitory activity against all hepatitis C virus (HCV) genotypes. A highly sensitive, simple, fast and specific one fluorometric method for determination of VLP in the presence of sofosbuvir was developed and validated. The fluorescence behavior of VLP in different organic solvents was examined and explained. Methanol was concluded to be the best sensitizing reagent. The native fluorescence intensity of VLP was accomplished at 383 nm with 339 nm for excitation wavelength. The impacts of experimental variables included pH, various organized media, and time of stability were examined and optimized. A linear relationship was achieved between the VLP concentration and the fluorescence intensity in a range of 5 to 5 × 10 3 ng mL -1 with 0.70 and 0.23 ng mL -1 , for quantitation and detection limits respectively. The proposed method was utilized for analyzing of VLP in human plasma and additionally expanded to examine the stability of VLP after its exposure to various stress conditions, like oxidative, alkaline, acidic, UV, daylight and sunlight conditions, according to ICH guidelines. Furthermore, the kinetics of acidic and oxidative degradations of VLP was examined. Moreover, the half-life times of the reaction (t 1/2 ) and the first-order reaction rate constants were estimated. Finally, a suggestion for the degradation pathway was presented., (© 2018 The Authors. Luminescence: The Journal of Biological and Chemical Luminescence published by John Wiley & Sons, Ltd.)

Two simple, selective and accurate methods were developed for the determination of Labetalol hydrochloride in pure form and pharmaceutical tablets. Both methods are based on derivatization of the studied drug with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBDCl) in alkaline medium (pH7.5).The reaction product was measured spectrofluorimetrically at 540nm after excitation at 476nm (method I) or spectrophotometrically at 480nm (method II). The calibration graphs were rectilinear over the concentration ranges of 0.10-2.0 and 1.0-11.0μgmL -1 for methods I and II, respectively. The proposed methods were successfully applied to the analysis of commercial tablets without interference from common excipients. Furthermore, the spectrofluorimetric method was utilized for the in vitro determination of labetalol in spiked human plasma, with a percent mean recovery (n=3) of 97.80±1.29%. Moreover, the spectrofluorimetric method was extended to examine the stability study of LBT under different stress conditions such as alkaline, acidic, oxidative, photolytic and a thermal degradation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We present a microfluidic platform for automatic multi-size spheroid formation within constant volume hanging droplets (HDs) from a single inlet loading of a constant cell concentration. The platform introduces three technological improvements over the existing spheroid formation platforms: 1) cell seeding control is achieved by enrichment of a cell solution rather than dilution; 2) cell seeding in each HD is fully independent and pre-programmable at the design stage; 3) the fabricated chip operates well using a hydrophobic PDMS surface, ensuring long-term storage possibility for device usage. Pre-programmed cell seeding densities at each HD are achieved using a "microfluidic funnel" layer, which has an array of cone-shaped wells with increasing apex angles acting as a metering unit. The integrated platform is designed to form, treat, stain, and image multi-size spheroids on-chip. Spheroids can be analyzed on-chip or easily transferred to conventional well plates for further processing. Empirically, enrichment factors up to 37× have been demonstrated, resulting in viable spheroids of diameters ranging from 230-420 μm and 280-530 μm for OV90 and TOV112D cell lines, respectively. We envision that microfluidic funnels and single inlet multi-size spheroid (SIMSS) chips will find broad application in 3D biological assays where size-dependent responses are expected, including chemoresponse assays, photodynamic therapy assays, and other assays involving drug transport characterization in drug discovery.

In cancer research and personalized medicine, new tissue culture models are needed to better predict the response of patients to therapies. With a concern for the small volume of tissue typically obtained through a biopsy, we describe a method to reproducibly section live tumor tissue to submillimeter sizes. These micro-dissected tissues (MDTs) share with spheroids the advantages of being easily manipulated on-chip and kept alive for periods extending over one week, while being biologically relevant for numerous assays. At dimensions below ~420 μm in diameter, as suggested by a simple metabolite transport model and confirmed experimentally, continuous perfusion is not required to keep samples alive, considerably simplifying the technical challenges. For the long-term culture of MDTs, we describe a simple microfluidic platform that can reliably trap samples in a low shear stress environment. We report the analysis of MDT viability for eight different types of tissues (four mouse xenografts derived from human cancer cell lines, three from ovarian and prostate cancer patients, and one from a patient with benign prostatic hyperplasia) analyzed by both confocal microscopy and flow cytometry over an 8-day incubation period. Finally, we provide a proof of principle for chemosensitivity testing of human tissue from a cancer patient performed using the described MDT chip method. This technology has the potential to improve treatment success rates by identifying potential responders earlier during the course of treatment and providing opportunities for direct drug testing on patient tissues in early drug development stages.