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Pholcodine, an anti-tussive medication widely used as an over-the-counter, OTC drug, has recently faced restrictions in several countries. This paper presents a sensitive electrochemical approach for pholcodine detection. The electrochemical method involved fabricating a graphene nanoplatelets electrode, incorporating polythiophene nanospheres polymer to promote electron transfer and increase the activated surface area. Characterization of the fabricated electrode was performed using transmission electron microscopy, ATR-Fourier-transform infrared spectroscopy, X-ray crystallography, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The electrochemical behavior of pholcodine with the fabricated electrode was investigated using cyclic voltammetry, chronoamperometry, square wave voltammetry (SWV), and differential pulse voltammetry (DPV). The developed electrode led to a linear response for pholcodine ranging from 10 to 45 mg/L with detection limits of 1.41 and 1.51 mg/mL for SWV and DPV, respectively and quantification limits of 4.27 and 4.57 mg/L for SWV and DPV, respectively. The proposed method has accurately recovered pholcodine in spiked serum samples with a recovery percentage ranging from 1.2 to 2.9%. The optimized method is found to be accurate, precise, and robust by applying validation parameters provided by International Council for Harmonization. Two green metrics were computed to assess the method's greenness, the findings showed that the developed method is environmentally friendly with minimum sample preparation steps., (© 2024. The Author(s).)

Two accurate, sensitive, and selective methods for simultaneous determination of miconazole nitrate (MIC), nystatin (NYS), and metronidazole (MET) in pure state or drug product were established and verified. First, RP-HPLC-DAD was designed. Separation was accomplished using a ZOBRAX Eclipse Plus RP-C 8 column that was running under an isocratic elution of methanol: 0.05% aqueous solution of sodium dodecyl sulphate (40: 60 v/v), with a flow rate that was regulated at 0.8 mL/min. The column temperature was adjusted at 25 °C and diode array detector was monitored at 220 nm. The linearity range of the proposed method was achieved at the concentration of 5-50, 4-50, and 4-40 µg/mL and the attained retention time for the studied drugs was 2.52, 3.52 and 4.99 min for MIC, NYS, and MET, correspondingly. Second, a TLC-densitometric approach was used to resolve the three compounds. Resolution of the three cited drugs was carried out using TLC aluminum plates pre-coated with 0.25 mm silica gel 60 F 254 . A developing solvent comprised ethyl acetate: toluene: methanol: triethyl amine: formic acid (3: 1: 7: 0.3: 0.1 by volume) (pH = 5.5) was utilized and scanning of the resolved bands at 215 nm. Linearity of the developed TLC method was evaluated and evident to be 0.4-2, 0.4-2.2, and 0.4-2 μg/band for MIC, NYS, and MET, in that order. The suggested chromatographic methods were verified according to ICH directives. The findings of the developed chromatographic procedures were statistically compared with the results of the reported ones using student's t-test and F-test. Furthermore, two green assessment tools evaluated the indicated methods' level of greenness (GAPI and AGREE)., (© 2023. The Author(s).)

The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and meclizine HCl (MEC) in a quinary mixture with two related impurities: the CYC main impurity, Benzhydrol (BEH), which has carcinogenic and hepatotoxic effects, and the MEC official impurity, 4-Chlorobenzophenone (BEP). The proposed augmented CLS models are orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS), and net analyte processing CLS (NAP-CLS). These models were applied to quantify the three active constituents in their raw materials and their corresponding dosage forms using their UV spectra. To evaluate the CLS-based models sensibly, we design a comparative study involving two sets: the training set to construct models and the validation set to assess the prediction abilities of these models. A five-level, five-factor calibration design was established to produce 25 mixtures for the calibration set. In addition, 16 experiments were performed for a test set distributed equally between the in-space and out-space samples. The primary criterion for comparing the models' performance was the validation set's root mean square error of prediction (RMSEP) value. Finally, augmented CLS models showed acceptable results for assaying the three analytes. The results were compared statistically with the reported HPLC methods; however, the DOSC-CLS model proved the best for assaying the dosage forms.

Research targeting natural cosmeceuticals is now increasing due to the safety and/or limited side effects of natural products that are highly valued in cosmetology. Within a research program exploring botanical sources for valuable skincare antioxidant components, the current study investigated the phytochemical content and the biological potential of Faucaria tuberculosa . Phytochemical investigation of F. tuberculosa extract resulted in purification and characterization of six phytoconstituents, including a new one. The structure of the new constituent was elucidated as (-) catechin-(2→1',4→2')-phloroglucinol ( 4 ). The structural identity of all isolated compounds were confirmed on the basis of extensive physical and spectral (1D, 2D-NMR and HRESIMS) investigations. The ethanolic extract exhibits a rich content of total phenolics (TPC) and total flavonoids (TFC), estimated as 32 ± 0.034 mg GAE/g and 43 ± 0.004 mg RE/g, respectively. In addition, the antioxidant (ABTS and FRAP), antihyaluronidase and antityrosinase activities of all purified phytoconstituents were evaluated. The results noted (-) catechin-(2→1',4→2') phloroglucinol ( 4 ) and phloroglucinol ( 1 ) for their remarkable antioxidant activity, while isorhamnetin 3- O -rutinoside ( 3 ) and 3,5-dihydroxyphenyl β -D-glucopyranoside ( 2 ) achieved the most potent inhibitory activity against tyrosinase (IC 50 22.09 ± 0.7 µM and 29.96 ± 0.44 µM, respectively) and hyaluronidase enzymes (IC 50 49.30 ± 1.57 µM and 62.58 ± 0.92, respectively) that remarkably exceeds the activity of the standard drugs kojic acid (IC 50 = 65.21 ± 0.47 µM) and luteolin, (IC 50 = 116.16 ± 1.69 µM), respectively. A molecular docking study of the two active compounds ( 3 and 2 ) highlighted their high potential to bind to the active sites of the two enzymes involved in the study.

This work aimed to develop and produce lacosamide-loaded niosomes coated with chitosan (LCA-CTS-NSM) using a thin-film hydration method and the Box-Behnken design. The effect of three independent factors (Span 60 amount, chitosan concentration, and cholesterol amount) on vesicle size, entrapment efficiency, zeta potential, and cumulative release (8 h) was studied. The optimal formulation of LCA-CTS-NSM was chosen from the design space and assessed for morphology, in vitro release, nasal diffusion, stability, tolerability, and in vivo biodistribution for brain targeting after intranasal delivery. The vesicle size, entrapment, surface charge, and in vitro release of the optimal formula were found to be 194.3 nm, 58.3%, +35.6 mV, and 81.3%, respectively. Besides, it exhibits sustained release behavior, enhanced nasal diffusion, and improved physical stability. Histopathological testing revealed no evidence of toxicity or structural damage to the nasal mucosa. It demonstrated significantly more brain distribution than the drug solution. Overall, the data is encouraging since it points to the potential for non-invasive intranasal administration of LCA as an alternative to oral or parenteral routes., Competing Interests: The authors wish to declare no interest is involved in this publication., (© 2023 The Authors. Published by Elsevier B.V.)

Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (-32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.

Quetiapine (QP) is a second-generation short-acting antipsychotic drug extensively metabolized in the liver, producing pharmacologically inactive metabolites and leading to diminished bioavailability. Therefore, this study aimed to develop an intravenous QP albumin nanoparticles (NPs) system for improving QP antipsychotic activity and brain targeting. QP-loaded albumin NPs were prepared by the desolvation method. The fabricated NPs were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. In vivo pharmacokinetics and biodistribution in rats were studied. In addition, the antipsychotic activity of the optimized platform was also investigated. Human serum albumin (HSA) concentration, pH, and stirring time were modulated to optimize QP albumin NPs with a particle size of 103.54 ± 2.36 nm and a QP EE% of 96.32 ± 3.98%. In addition, the intravenous administration of QP albumin NPs facilitated QP brain targeting with a 4.9-fold increase in targeting efficiency compared to the oral QP solution. The QP albumin NPs improved the QP antipsychotic activity, indicated by suppressing rats' hypermobility and reducing the QP's extrapyramidal side effects. The obtained results proposed that intravenous QP- NPs could improve QP brain targeting and its antipsychotic efficiency.

The feasibility of using lipid-polymer hybrid (LPH) nanocarriers as a potential platform for the intranasal delivery of ziprasidone (ZP), a second-generation antipsychotic, was explored. Different ZP-loaded LPH composed of a PLGA core and cholesterol-lecithin lipid coat were prepared using a single step nano-precipitation self-assembly technique. Modulation of polymer, lipid and drug amounts, as well as stirring-speed-optimized LPH with a particle size of 97.56 ± 4.55 nm and a ZP entrapment efficiency (EE%) of 97.98 ± 1.22%. The brain deposition and pharmacokinetics studies proved the efficiency of LPH to traverse the blood-brain barrier (BBB) following intranasal delivery with a 3.9-fold increase in targeting efficiency compared to the intravenous (IV) ZP solution with a direct nose-to-brain transport percentage (DTP) of 74.68%. The ZP-LPH showed enhanced antipsychotic activity in terms of animals' hypermobility over an IV drug solution in schizophrenic rats. The obtained results showed that the fabricated LPH was able to improve ZP brain uptake and proved its antipsychotic efficiency.

Antibacterial resistance bears a major threat to human health worldwide, causing about 1.2 million deaths per year. It is noteworthy that carbazole derivatives have shown a potential antibacterial activity, for example, 9-methoxyellipticine, which was isolated from Ochrosia elliptica Labill. roots (Apocynaceae) in the present study. An in vitro screening of the antibacterial activity of 9-methoxyellipticine was investigated against four multidrug-resistant (MDR) Klebsiella pneumoniae and Shiga toxin-producing Escherichia coli (STEC O157) as Gram-negative bacteria, in addition to Methicillin-resistant Staphylococcus aureus (MRSA) with Bacillus cereus as Gram-positive bacteria. The compound had significant antibacterial activity against the two Gram-negative isolates and lower activity against the Gram-positive ones. The synergistic use of 9-methoxyellipticine and antibiotics was successfully effective in reducing the MDR microorganisms. Lung pneumonia and kidney infection mice models were used to investigate the compound's efficacy in vivo for the first time. Noteworthy reductions in K. pneumoniae and STEC shedding and the colonization were observed, with a reduction in pro-inflammatory factors and immunoglobulin levels. Other related lesions such as inflammatory cell infiltration, alveolar interstitial congestion, and edema were noticed to occur, lessened to different limits. The anti-STEC and anti- K. pneumoniae activities of 9-methoxyellipticine were revealed, providing a new alternative against MDR nosocomial infections.

Multidrug resistance (MDR) pathogens are usually associated with higher morbidity and mortality rates. Flavonoids are good candidates for the development of new potential antimicrobials. This research investigated whether luteolin 4'-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae , fos A-positive shiga toxin producing the Escherichia coli serogroup O111 (STEC O111), and Bacillus cereus . In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), anti- K. pneumoniae (MIC of 53.33 ± 8.47 µg/mL) and anti-STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of B. cereus , the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in K. pneumoniae and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-α), and immunoglobulin (IgM). Additionally, the renal and pulmonary lesions were remarkably enhanced, with a significant decrease in the bacterial loads in the tissues. Finally, this study presents L4N as a potent substitute for traditional antibiotics with anti-STEC O111 and anti- K. pneumoniae potential, a finding which is reported here for the first time.

India has already passed through 2 waves of the coronavirus disease (COVID-19) pandemic losing many lives. The reason for losing lives may be due to the unpreparedness of the health care system of India for this unprecedented pandemic. To assess the government's preparedness, an institutional-based cross-sectional prospective survey was conducted among the adult population of selected states in India. A self-administered 30-item questionnaire divided into 5 sections (demography of the participants, steps to create awareness, prevent spread of infection, handle the emergency, and prognosis) was distributed online through Google Forms. The responses were collected in an Excel file. SPSS software was used to perform the descriptive statistics and analysis of variance (ANOVA). Nearly a quarter of the participants "strongly disagree"/"disagree" about the government's preparedness for the third wave. Considering their perception, it cannot be assured that the government is well prepared to handle the emergency. So, the government must maintain emergency funding and develop a health infrastructure. The government should take steps to reduce social stigma, prevent spreading of unscientific propagation, and make people aware of the World Health Organization (WHO) as the reliable source of information for health emergencies to avoid a human crisis in the future.

Introduction: Coronavirus disease 2019 (COVID-19) results in similar clinical characteristics as bacterial respiratory tract infections and can potentially lead to antibiotic overuse. This study aimed to determine the changes in hospital antimicrobial usage before and during the COVID-19 pandemic., Methodology: We compared antimicrobial consumption data for 2019 and 2020. Inpatient antibiotic consumption was determined and expressed as a defined daily dose (DDD) per 100 occupied bed days, following the World Health Organization (WHO) methods. The WHO Access, Watch, and Reserve (AWaRe) classification was used., Results: The total antimicrobial consumption in 2020 increased by 16.3% compared to consumption in 2019. In 2020, there was a reduction in fourth-generation cephalosporins (-30%), third-generation cephalosporins (-29%), and combinations of penicillins (-23%). In contrast, antibiotics that were consumed more during 2020 compared with 2019 included linezolid (374%), vancomycin (66.6%), and carbapenem (7%). Linezolid is the only antibiotic from the Reserve group on the hospital's formulary. Antibiotic usage from the Access group was reduced by 17%, while antibiotic usage from the Watch group and the Reserve group was increased by 3% and 374%, respectively., Conclusions: The findings show a significant shift in antibiotic usage from the Access group to the Watch and Reserve groups. The Watch and Reserve groups are known to be associated with increased resistance to antibiotics. Therefore, antimicrobial stewardship should be increased and maintained during the pandemic to ensure appropriate antibiotic use., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Raghda RS Hussein, Al Shaimaa Ibrahim Rabie, Maryam Bin Shaman, Ahmed Hassan Shaaban, Alzhraa M Fahmy, Mahmoud R Sofy, Elizabeth A Lattyak, Ahmed Abuelhana, Ibrahim A Naguib, Ahmed M Ashour, Mamoon A Aldeyab.)

Indomethacin is a widely used nonsteroidal anti-inflammatory drug; however, its clinical utility is accompanied by serious adverse reactions including peptic ulcers. The current study aims to investigate the protective potential of perindopril against indomethacin-induced gastric injury in rats. Perindopril (4 mg/kg) was administered orally for 7 days and indomethacin (60 mg/kg, single oral dose) was administered on the 7 th day, 1 h after perindopril administration. Pantoprazole was used as a standard agent. Ulcer index (UI), preventive index ratio (PI), histopathological examination, oxidative stress, and inflammatory biomarkers were investigated. Perindopril significantly decreased UI while increased PI and counteracted histopathological aberrations induced by indomethacin. It alleviated indomethacin-induced oxidative stress by lowering NO while increasing GSH content and superoxide dismutase activity. Perindopril significantly downregulated TNF-α and asymmetric dimethylarginine (ADMA), while significantly upregulated COX-2, PGE-2, dimethylarginine dimethylaminohydrolase-1 (DDAH-1), ANG-(1-7), and ACE-2 expression. Together, these findings suggest the gastroprotective effects of perindopril through modulation of DDAH-1/ADMA and ACE-2/ANG-(1-7) signaling.HIGHLIGHTSPerindopril attenuated gastric histopathological damage.It increased GSH content and SOD activity while decreased NO content.It modulated gastric ADMA and DDAH-1 activity.It reduced TNF-α, while increased COX-2 and PGE-2 expression.It upregulated ACE-2 activity and ANG-(1-7) protein expression.

Aim: This study is aimed at evaluating the use of curcumin-loaded polylactic-co-glycolic acid nanoparticles (CUR-loaded PLGA NPs) as a treatment against monosodium iodoacetate- (MIA-) induced knee OA., Materials and Methods: Eighteen rats were assigned to three groups ( n = 6), namely, normal control group that received intra-articular injections (IAIs) of saline, an OA control group that received an IAIs of MIA (2 mg/50  μ L), and a treatment group (MIA+CUR-loaded PLGA NPs) that received IAIs of CUR-loaded PLGA NPs (200 mg/kg b.wt)., Results: The CUR NP treatment against knee OA alleviated radiographic alternations and histopathological changes and inhibited the upregulation in the serum levels of interleukin-1 β , tumor necrosis factor- α , interleukin-6, and transforming growth factor-beta and the downregulation in interleukin-10. CUR NP-treated joints also decreased the mRNA expression of nuclear factor-kappa B and inducible nitric oxide synthase and the protein expression of matrix metalloproteinase-13 and caspase-3. Finally, CUR-loaded PLGA NP treatment mitigated the loss of type II collagen, which resulted in a significant reduction in malondialdehyde level and increased the glutathione content and superoxide dismutase activity compared with that of the OA group., Conclusion: This study demonstrated that the administration of CUR NPs could provide effective protection against MIA-induced OA and knee joint histological deteriorated changes due to its anti-inflammatory, antioxidant, and antiapoptotic properties., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Hadeer M. Hamdalla et al.)

Interest in plant-based diets has been on the rise in recent years owing to the potential health benefits of their individual components and the notion that plant-based diets might reduce the incidence of several diseases. Egyptian dukkah and Syrian za'atar are two of the most historic and famous Middle Eastern herbal blends used for their anti-inflammatory, hypolipidemic, and antidiabetic effects. Headspace SPME-GCMS and HPLC-DAD were adopted for characterizing the aroma profile and phenolic compounds of both herbal blends, respectively. Further, vapor-phase minimum inhibitory concentration was employed for assessing each blend's antibacterial potential, while their antioxidant potential was estimated via in vitro antioxidant assays. SPME headspace analysis indicated the abundance of ethers and monoterpene hydrocarbons, while HPLC revealed the presence of several phenolics including rosmarinic acid, ferulic acid, and rutin. Biological investigations affirmed that vapor-phase of the tested blends exhibited antibacterial activities against Gram-positive and Gram-negative pathogens, while the antioxidant potential of the blends was investigated and expressed as Trolox (125.15 ± 5.92 to 337.26 ± 13.84 μM T eq/mg) and EDTA (18.08 ± 1.62 to 51.69 41 ± 5.33 μM EDTA eq/mg) equivalent. The presented study offers the first insight into the chemical profile and biological activities of both dukkah and za'atar.

The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided into three groups—a control group (n = 33) with no statin treatment, an atorvastatin group (n = 33) with a single 80 mg atorvastatin dose and the rosuvastatin group (n = 33) with a single 40 mg rosuvastatin dose in the emergency room (ER) prior to PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were recorded, and ST-segment resolution was measured. Results: CTFC was significantly lower for the atorvastatin group (p-value < 0.01) than in the control group. A final TIMI flow grade 3 was achieved in 32 (97.0%) patients in the rosuvastatin group and 28 (84.8%) patients in the atorvastatin group compared with only 25 (75.8%) patients in the control group (p = 0.014). Peak CK-MB in the rosuvastatin group (263.2 [207.2−315.6]) and the atorvastatin group (208 [151.0−314.1]) was lower compared to that in the control group (398.4 [303.9−459.3]); p < 0.001. Conclusions: A single extensive dose of lipophilic atorvastatin prior to primary PCI in STEMI patients showed better improvement in microvascular myocardial perfusion compared to hydrophilic rosuvastatin.

Naftazone is a quinone-semi carbazone drug that possesses a strong orange color, and hence it was usually analyzed colorimetrically or by HPLC-UV. However, these methods are not sensitive enough to determine naftazone in biological samples. Naftazone lacks intrinsic fluorescence and does not possess easily derivatizable functional groups. In this contribution, we introduced the first spectrofluorimetric method for naftazone assay through reduction-elicited fluorogenic derivatization through the reduction of its quinone-semicarbazone moiety to the corresponding quinol-semicarbazide derivative by potassium borohydride as a reduction probe. The solvent-dependent fluorescence of the reaction product was studied in various protic and aprotic solvents. Eventually, the fluorescence of the reduced naftazone was measured in 2-propanol at λ emission of 350 nm after excitation at λ ecxitation of 295 nm. The relative fluorescence intensity was linearly correlated to the drug concentration (r = 0.9995) from 10.0 to 500 ng/mL with high sensitivity, where the lower detection limit was 2.9 ng/mL. Hence, the method was effectively applied for naftazone tablets quality control with a mean %recovery of 100.3 ± 1.5, and the results agreed with those of the comparison HPLC-UV method. Furthermore, a new salting-out assisted liquid-liquid extraction (SALLE) method was established for naftazone extraction from human serum, followed by its determination using the developed reduction-based fluorogenic method. The developed SALLE method showed excellent recovery for naftazone from human serum (92.3-106.5%) with good precision (RSD ≤ 6.8%). Additionally, the reaction of naftazone with potassium borohydride was kinetically monitored, and it was found to follow pseudo-first-order kinetics with an activation energy of 43.8 kcal/mol. The developed method's greenness was approved using three green analytical chemistry metrics.

Osteoarthritis (OA) of the knee is a debilitating condition that can severely limit an individual's mobility and quality of life. This study was designed to evaluate the efficacy of bone marrow-derived mesenchymal stem cell (BM-MSC) treatment in cartilage repair using a rat model of monoiodoacetate- (MIA-) induced knee OA. OA was induced in the knee joint of rats by an intracapsular injection of MIA (2 mg/50  μ L) on day zero. The rats were divided into three groups ( n = 6): a normal control group, an osteoarthritic control group, and an osteoarthritic group receiving a single intra-articular injection of BM-MSCs (5 × 10 6 cells/rat). The knee diameter was recorded once per week. By the end of the performed experiment, X-ray imaging and enzyme-linked immunosorbent assay analysis of serum inflammatory cytokines interleukin-1beta (IL- β ), IL-6, and tumor necrosis factor- α (TNF- α ) and anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta (TGF- β ) were carried out. In addition, RT-PCR was used to measure nuclear factor-kappa B (NF- κ B), inducible nitric oxide synthase (iNOS), and type II collagen mRNA levels and Western blot analysis was used to determine caspase-3 protein levels in all treated groups. Finally, hematoxylin/and eosin stains were used for histopathological investigation. Administration of BM-MSCs significantly downregulated knee joint swelling and MIA-induced (IL-1 β , IL-6, and TNF- α ) and upregulated IL-10 and TGF- β as well. Moreover, BM-MSC-treated osteoarthritic rats exhibited decreased expression of NF- κ B, iNOS, and apoptotic mediator (caspase-3) and increased expression of type II collagen when compared to rats treated with MIA alone. The hematoxylin/eosin-stained sections revealed that BM-MSC administration ameliorated the knee joint alterations in MIA-injected rats. BM-MSCs could be an effective treatment for inflamed knee joints in the MIA-treated rat model of osteoarthritis, and the effect may be mediated via its anti-inflammatory and antioxidant potential., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Hadeer Mohamed Hamdalla et al.)

These days, many efforts have been made to increase and develop the solubility and bioavailability of novel therapeutic medicines. One of the most believable approaches is the operation of supercritical carbon dioxide fluid (SC-CO 2 ). This operation has been used as a unique method in pharmacology due to the brilliant positive points such as colorless nature, cost-effectives, and environmentally friendly. This research project is aimed to mathematically calculate the solubility of Oxaprozin in SC-CO 2 through artificial intelligence. Oxaprozin is a nonsteroidal anti-inflammatory drug which is useful in arthritis disease to improve swelling and pain. Oxaprozin is a type of BCS class II (Biopharmaceutical Classification) drug with low solubility and bioavailability. Here in order to optimize and improve the solubility of Oxaprozin, three ensemble decision tree-based models including random forest (RF), Extremely random trees (ET), and gradient boosting (GB) are considered. 32 data vectors are used for this modeling, moreover, temperature and pressure as inputs, and drug solubility as output. Using the MSE metric, ET, RF, and GB illustrated error rates of 6.29E-09, 9.71E-09, and 3.78E-11. Then, using the R-squared metric, they demonstrated results including 0.999, 0.984, and 0.999, respectively. GB is selected as the best fitted model with the optimal values including 33.15 (K) for the temperature, 380.4 (bar) for the pressure and 0.001242 (mole fraction) as optimized value for the solubility., (© 2022. The Author(s).)

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF- α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Osama M. Ahmed et al.)

A validated RP-HPLC method was developed for the estimation of paracetamol, caffeine, metoclopramide and ergotamine simultaneously in bulk and pharmaceutical formulation. The method was extended for the determination of two paracetamol genotoxic and nephrotoxic impurities and degradation products namely p-aminophenol and 4-chloroacetanilide. Separation was done on octadecyl column (15 cm × 2.1 mm, 5 μm). Gradient elution was performed using mobile phase consisting of acetonitrile and water (pH 3) in ratio of (20: 80, v/v) for the first 3 min, (50: 50, v/v) for the next 4.5 min, then (20: 80, v/v) for the final 2.5 min. The flow rate was 0.7 mL/min throughout the run which took 10 min. UV detection was done at 230 nm. The proposed method agreed with ICH guidelines of method validation. The suggested method was applied for the estimation of the proposed drugs in their dosage form. Statistical comparison was done between the results obtained from the suggested method and those obtained from reported HPLC method. The proposed method is more beneficial than the published one because of having higher sensitivity and selectivity as it allows the detection of the proposed drugs in lower concentrations in the presence of paracetamol toxic impurities, p-aminophenol and 4-chloroacetanilide., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Industrial-based application of supercritical CO 2 (SCCO 2 ) has emerged as a promising technology in numerous scientific fields due to offering brilliant advantages, such as simplicity of application, eco-friendliness, and high performance. Loxoprofen sodium (chemical formula C 15 H 18 O 3 ) is known as an efficient nonsteroidal anti-inflammatory drug (NSAID), which has been long propounded as an effective alleviator for various painful disorders like musculoskeletal conditions. Although experimental research plays an important role in obtaining drug solubility in SCCO 2 , the emergence of operational disadvantages such as high cost and long-time process duration has motivated the researchers to develop mathematical models based on artificial intelligence (AI) to predict this important parameter. Three distinct models have been used on the data in this work, all of which were based on decision trees: K-nearest neighbors (KNN), NU support vector machine (NU-SVR), and Gaussian process regression (GPR). The data set has two input characteristics, P (pressure) and T (temperature), and a single output, Y = solubility. After implementing and fine-tuning to the hyperparameters of these ensemble models, their performance has been evaluated using a variety of measures. The R-squared scores of all three models are greater than 0.9, however, the RMSE error rates are 1.879 × 10 -4 , 7.814 × 10 -5 , and 1.664 × 10 -4 for the KNN, NU-SVR, and GPR models, respectively. MAE metrics of 1.116 × 10 -4 , 6.197 × 10 -5 , and 8.777 × 10 -5 errors were also discovered for the KNN, NU-SVR, and GPR models, respectively. A study was also carried out to determine the best quantity of solubility, which can be referred to as the (x 1 = 40.0, x 2 = 338.0, Y = 1.27 × 10 -3 ) vector.

Like most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities to both the cell receptor and the drugs targeting such a protein. The current study intended to assess the ability of different variants of interest (VOIs) and variants of concern (VOCs) of SARS-CoV-2 for their affinities of binding to different repurposed drugs. Seven FDA approved drugs, namely, camostat, nafamostat mesylate, fenofibrate, umifenovir, nelfinavir, cefoperazone and ceftazidime, were selected based on their reported in vitro and clinical activities against SARA-CoV-2. The S1 protein subunit from eleven different variants, including the latest highly contiguous omicron variant, were used as targets for the docking study. The docking results revealed that all tested drugs possess moderate to high binding energies to the receptor-binding domain (RBD) of the S1 protein for all different variants. Cefoperazone was found to possess the highest binding energy to the RBD of the S1 protein of all the eleven variants. Ceftazidime was the second-best drug in terms of binding affinity towards the S1 RBD of the investigated variants. On the other hand, fenofibrate showed the least binding affinity towards the RBD of the S1 protein of all eleven variants. The binding affinities of anti-spike drugs varied among different variants. Most of the interacting amino acid residues of the receptor fall within the RBD (438-506).

This research aimed to boost granisetron (GS) delivery to the brain via the intranasal route to better manage chemotherapy-induced emesis. Glycerol monooleate (GMO), Poloxamer 407 (P 407) and Tween 80 (T 80) were used to formulate GS-loaded cubosomes (GS-CBS) utilizing a melt dispersion-emulsification technique. GS-CBS were characterized by testing particle diameter, surface charge and entrapment efficiency. The formulations were optimized using a Box-Behnken statistical design, and the optimum formula (including GMO with a concentration of 4.9%, P 407 with a concentration of 10%, and T 80 with a concentration of 1%) was investigated for morphology, release behavior, ex vivo permeation through the nasal mucosa, and physical stability. Moreover, the optimal formula was incorporated into a thermosensitive gel and subjected to histopathological and in vivo biodistribution experiments. It demonstrated sustained release characteristics, increased ex vivo permeability and improved physical stability. Moreover, the cubosomal in situ gel was safe and biocompatible when applied to the nasal mucosa. Furthermore, compared to a drug solution, the nose-to-brain pathway enhanced bioavailability and brain distribution. Finally, the cubosomal in situ gel may be a potential nanocarrier for GS delivery to the brain through nose-to-brain pathway.

Sixteen compounds ( TR1-TR16 ) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC 50 value of 0.17 μM, followed by TR2 (IC 50 = 0.27 μM). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para -chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with K i values of 0.230 ± 0.004 and 0.149 ± 0.016 µM, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.

Cyclizine hydrochloride (CYC) and meclozine hydrochloride (MEC) are antihistaminic drugs generally co-formulated with pyridoxine hydrochloride (PYR) to treat nausea and vomiting in pregnancy. Several analytical techniques have been applied for the determination of CYC or MEC with PYR, but determination of CYC impurity; benzhydrol (BEH) or MEC impurity; or 4-chlorobenzophenone (BEP) has not been paid attention to. Therefore, micellar UPLC method is introduced for analysis of ternary mixtures containing PYR together with both CYC and BEH (mixture I) or MEC and BEP (mixture II). Chromatographic separation was achieved using a Hypersil gold C 8 column (50 × 2.1 mm, 1.9 μm) using 0.01 M sodium dodecyl sulfate modified to pH 3.5 using phosphoric acid:acetonitrile (45:55 by volume) for mixture I and 0.1% sodium dodecyl sulfate, 0.1% sodium bicarbonate adjusted to pH 2.6 by phosphoric acid:acetonitrile (47:53 by volume) for mixture II as mobile phases. The separated peaks were detected at 230 and 245 nm for mixtures I and II, respectively. The adopted methods were validated in conformance with the International Conference on Harmonization (ICH) recommendations and were properly applied in commercial pharmaceutical formulation analysis. Comprehensive ecological comparison was achieved, confirming a higher ecological value of the presented methods compared to the earlier reported methods., (© 2022 John Wiley & Sons, Ltd.)

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcers represent a significant clinical concern and adversely affect the quality of life. Inducible nitric oxide synthase/endothelial nitric oxide synthase (iNOS/eNOS) and asymmetric dimethylarginine/ dimethylarginine dimethylaminohydrolase-1 (ADMA/DDAH-1) signaling are key players in gastric ulcer pathogenesis. This work was planned to explore the role of iNOS/eNOS and ADMA/DDAH-1 signaling in rats with indomethacin-induced gastric ulcer, as potential pathways for the gastro-protective effect of tadalafil. Split into 5 separate groups, rats were assigned to control, tadalafil (10 mg/kg, p.o), indomethacin (single oral dose of 60 mg/kg), indomethacin + pantoprazole (40 mg/kg, p.o), and indomethacin + tadalafil (10 mg/kg, p.o). The results indicated that pretreatment with tadalafil significantly reduced ulcer index (UI), increased preventive index (PI), and counteracted indomethacin-induced histopathological aberrations. Tadalafil significantly reduced the gastric content of NO while it significantly elevated that of GSH and enhanced SOD activity. It significantly reduced the gastric expression of TNF-α and ADMA while it significantly elevated that of COX-2, PGE-2, and DDAH-1. Western blot analysis revealed that pretreatment with tadalafil significantly reduced iNOS protein expression while it significantly elevated that of eNOS. Collectively, these data suggest that tadalafil exerts potential protective effect against indomethacin-induced ulcer through suppression of inflammation, attenuation of oxidative stress, and boosting of antioxidants. Moreover, tadalafil protective effects are mediated via upregulation of PGE-2 with modulating the signaling pathways of ADMA/DDAH-1, and iNOS/eNOS. As a result, the current evidence corroborates the use of tadalafil in controlling gastric ulcers and preventing NSAID gastric side effects., (Copyright © 2022. Published by Elsevier Masson SAS.)

For a variety of applications, the brass alloy has been utilized to replace titanium tubes in heat exchangers. Copper alloys' high corrosion rate during the acid cleaning procedure remains a significant concern. To inhibit the corrosion of brass alloys, we prepared two novel gemini surfactants (GSs), N 1 , N 3 -dibenzyl- N 1 , N 1 , N 3 , N 3 -tetramethylpropane-1,3-diaminium tetrafluoroborate (I H) and N 1 , N 1 , N 3 , N 3 -tetramethyl- N 1 , N 3 -bis (4-methyl benzyl) propane-1,3-diaminium tetrafluoroborate (I Me), and they were characterized using Fourier transform infrared spectroscopy and 1 H nuclear magnetic resonance spectroscopy. Their inhibition performance against corrosion of brass alloys in 1 M HCl was studied using electrochemical techniques including potentiodynamic polarization (PP), electrochemical impedance spectroscopy, and electrochemical frequency modulation. The inhibition effect of the synthesized compounds was high, and it increased as the inhibitor's concentration was increased. The maximum level of inhibition efficiency was achieved at an inhibitor concentration of 100 ppm, reaching 96.42% according to PP measurements. From Langmuir data, the mechanisms of adsorption of the two GSs on the surface of copper was found to be physisorption and chemisorption adsorption. X-ray photoelectron spectroscopy and scanning electron microscopy show that the addition of the two compounds lowers the dissolution of brass ions in the corrosive solution and forms a protective layer on the surface of the brass., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A variety of receptor and donor characteristics influence long-and short-term kidney graft survival. It is critical to predict the effectiveness of kidney transplantation to optimise organ allocation. This would allow patients to choose the best accessible kidney donor and the optimal immunosuppressive medication. Several studies have attempted to identify factors that predispose to graft rejection, but the results have been contradictory. As a result, the goal of this paper is to use the African buffalo-based artificial neural network (AB-ANN) approach to uncover predictive risk variables related to kidney graft. These two feature selection approaches combine to provide a novel hybrid feature selection technique that could select the most important elements to improve prediction accuracy. The feature analysis revealed that clinical features have varied effects on transplant survival. The collected data is processed in both training and testing methods. The prediction model's performance, in terms of accuracy, precision, recall, and F-measure, was examined, and the results were compared with those of other existing systems, including naive Bayesian, random forest, and J48 classifier. The results suggest that the proposed approach can forecast graft survival in kidney recipients' next visits in a creative manner and with more accuracy compared with other classifiers. This proposed method is more efficient for predicting kidney graft survival. Incorporating those clinical tools into outpatient clinics' everyday workflows could help physicians make better and more personalised decisions., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (Copyright © 2022 Riddhi Chawla et al.)

Remdesivir (REM) is considered the first therapeutic option approved by US Food and Drug Administration (FDA) for clinical care in case of hospitalized patients suffering in COVID-19 epidemic. In the presented multilateral comparative search, four eco friendlessness approaches -National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI), and Analytical Greenness metric (AGREE) are tested to assess 16 analytical chromatographic procedures reported for the analysis of the commonly used antiviral drug; Remdesivir (REM). The values of testing more than one approach when estimating the eco-friendly characters for analytical methods are illustrated in this study. On the light of the outcomes, ESA and AGREE approaches are recommended as they are easily applied and digitally presented. Furthermore, GAPI is also a reliable tool in terms of comprehensiveness for the whole analytical procedures, from sampling till the final assessment. NEMI is the easiest and fastest greenness evaluation tool; however, the information it provides is particularly of limited scope and sometimes inaccurate. To ensure greenness of chromatographic analytical methods, there must be clear planning beforehand, to reduce chemical hazards sent to environment. Additionally, it is highly recommended in method validation protocols to consider the greenness of a given analytical procedure before releasing to routine use. The LC-MS/MS analysis for the active metabolite of REM (Nuc) reported by Avataneo et al. and Du et al. proved to be the best bio-analytical methods regarding the environmental aspects depending on the GAPI and AGREE tools. However, the HPLC method for REM analysis in intravenous solution reported by Jitta et al. proved to be the greenest analytical method for determination of REM in the pharmaceutical dosage forms according to the ESA, GAPI, and AGREE tools., Competing Interests: 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., (© 2022 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) represents around 85% of all known types of liver cancers and is estimated to be the fifth most common cause of cancer-related death worldwide. The current study assessed the preventive efficacy of isatin on diethylnitrosamine (DENA)/2-acetylaminofluorene (2-AAF)-induced hepatocarcinogenesis in male Wistar rats and investigated the underlying cellular and molecular mechanisms. HCC was initiated by intraperitoneal injection of DENA (150 mg/kg/week) for two weeks, followed by oral 2-AAF (20 mg/kg) every other day for three successive weeks. Oral isatin or vehicle (control) was administered at 25 mg/kg for 20 weeks during and following HCC induction. Isatin ameliorated the deleterious effects of DENA/2-AAF on liver function as evidenced by reduced serum levels of AST, ALT, total bilirubin, albumin, and liver tumor biomarkers (CA19.9 and AFP) compared to control DENA/2-AAF-treated rats. Histopathological evaluations demonstrated that isatin-mediated protection against hepatocarcinogenesis was accompanied by a decline in hepatic lipid peroxidation, a marker of oxidative stress, and enhanced antioxidant capacity, as evidenced by increased glutathione and superoxide dismutase expression. Isatin treatment also upregulated expression of the major stress-response transcription factor Nrf2 and the detoxifying enzymes NAD(P)H quinine oxidoreductase and glutathione-S-transferase alpha 2 and downregulated expression of the proliferation marker Ki67. Moreover, isatin significantly reduced the DENA/2-AAF-induced decrease in hepatic expression of anti-apoptotic Bcl2 and the DENA/2-AAF-induced increases in pro-inflammatory and pro-apoptotic factors (TNF-α, NF-κB p50, NF-κB p65, p53, and caspase 3). Thus, it can be concluded that isatin may protect against chemically induced hepatocarcinogenesis by enhancing cellular antioxidant, anti-inflammatory, and detoxification mechanisms, in part through upregulation of the Nrf2 signaling pathway.

Background: Noising is an undesirable phenomenon accompanying the development of widely used chemometric models such as partial least square regression (PLSR) and support vector regression (SVR)., Objective: Optimizations of these chemometric models by applying orthogonal projection to latent structures (OPLS) as a preprocessing step which is characterized by canceling noise is the purpose of this research study. Additionally, a comprehensive comparative study between the developed methods was undertaken highlighting pros and cons., Methods: OPLS was conducted with PLSR and SVR for quantitative determination of pyridoxine HCl, cyclizine HCl, and meclizine HCl in the presence of their related impurities. The training set was formed from 25 mixtures as there were five mixtures for each compound at each concentration level. Additionally, to check the validity and predictive ability of the developed chemometric models, independent test set mixtures were prepared by repeating the preparation of four mixtures of the training set plus preparation of another four independent mixtures., Results: Upon application of the OPLS processing method, an upswing of the predictive abilities of PLSR and SVR was found. The root-mean-square error of prediction of the test set was the basic benchmark for comparison., Conclusion: The major finding from the conducted research is that processing with OPLS reinforces the ability of models to anticipate the future samples., Highlights: Novel optimizations of the widely used chemometric models; application of a comparative study between the suggested methods; application of OPLS preprocessing methods; quantitative determination of pyridoxine HCl, cyclizine HCl and meclizine HCl; checking the predictive power of developed chemometric models; analysis of active ingredients in their pharmaceutical dosage forms., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUC brain /AUC blood , drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer's disease, through intranasal therapy.

Schizophrenia is a mental disorder characterized by alterations in cognition, behavior and emotions. Oral olanzapine (OZ) administration is extensively metabolized (~up to 40% of the administrated dose). In addition, OZ is a P-glycoproteins substrate that impairs the blood-brain barrier (BBB) permeability. To direct OZ to the brain and to minimize its systemic side effects, the nasal pathway is recommended. OZ-loaded polymeric micelles nano-carriers were developed using suitable biodegradable excipients. The developed micelles were physicochemically investigated to assess their appropriateness for intranasal delivery and the potential of these carriers for OZ brain targeting. The selected formula will be examined in vivo for improving the anti-schizophrenic effects on a schizophrenia rat model. The binary mixture of P123/P407 has a low CMC (0.001326% w / v ), which helps in maintaining the formed micelles' stability upon dilution. The combination effect of P123, P407 and TPGS led to a decrease in micelle size, ranging between 37.5-47.55 nm and an increase in the EE% (ranging between 68.22-86.84%). The selected OZ-PM shows great stability expressed by a suitable negative charge zeta potential value (-15.11 ± 1.35 mV) and scattered non-aggregated spherical particles with a particle size range of 30-40 nm. OZ-PM maintains sustained drug release at the application site with no nasal cytotoxicity. In vivo administration of the selected OZ-PM formula reveals improved CNS targeting and anti-schizophrenia-related deficits after OZ nasal administration. Therefore, OZ-PM provided safe direct nose-to-brain transport of OZ after nasal administration with an efficient anti-schizophrenic effect.

Migraine is one of the major symptoms of many psychiatric and mental disorders like depression and anxiety. Eletriptan Hydrobromide (EH) is a well-tolerated drug in migraine treatment, but suffers from low oral bioavailability and low brain targeting after oral delivery. New nasal mucoadhesive EH-emulsomes development could be a new means to direct the drug from the nose-to-brain to achieve rapid onset of action and high drug concentration in the brain for acute migraine treatment. Eletriptan mucoadhesive emulsomes formulations were prepared using thin-film hydration method and 2 3 full factorial design was adopted to study different formulation factors' effect on the emulsomes characters. The emulsomes were characterized for entrapment efficiency (EE%), zeta potential (ZP), particle size (PS), morphology, and ex-vivo permeation through the nasal mucosa. The selected formula was evaluated in mice for its in-vivo bio-distribution in comparison with EH intranasal and intravenous solutions. Drug targeting efficacy (DTE%) and nose-to-brain direct transport percentage (DTP%) were calculated. The optimization formulation showed a nanoparticle size of 177.01 nm, EE 79.44%, and ZP = 32.12 ± 3.28 mV. In addition, in-vitro permeability studies revealed enhanced drug permeability with suitable mean residence time up to 120 ± 13 min. EH-emulsomes were stable under different storage conditions for three months. In vivo examination and pharmacokinetic drug targeting parameters revealed EH transport to the CNS after EH nanoparticle nasal administration. Histopathology study showed no ciliotoxic effect on the nasal mucosa. From the results, it can be confirmed that the emulsomes formulation of EH proved safe direct nose-to-brain transport of EH after nasal administration of EH emulsomes.

Background: Extraction is the leading critical stage in the analysis of nutraceuticals. Ginkgo biloba (GB) has gained interest because of its therapeutic usages., Objectives: The aim was to develop four cost-effective extraction techniques for the extraction of quercetin from GB in a sachet containing a mixture of nutraceuticals. These techniques are solid-phase extraction (SPE), liquid-liquid extraction, inverted dispersive liquid-liquid microextraction, and the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method., Method: Direct spectrophotometry was used to monitor the recovery of the standard quercetin throughout the optimization steps. The HPLC-UV method of analysis was optimized to quantify the yields from the extracts present in the complicated contents of the sachets. The present study was assessed by analytical Eco-Scale assessment (ESA) and the National Environmental Method Index (NEMI) for greenness in comparison with the literature., Results: SPE showed the best cleanup outcomes. ESA and NEMI showed an adequate greenness of the proposed extraction protocol., Conclusions: Quercetin (marker for GB) extraction from market nutraceutical sachets is considered an exemplar for analysis in the QC of nutraceuticals. Regarding the greenness results, the proposed method of extraction is better even with adequate greenness as the extraction was a one-step process, in comparison with multistep processes of previously published protocols. Accordingly, it is recommended for use in routine extraction and analysis of such nutraceuticals., Highlights: Four extraction protocols have been developed. For GB ternary-mixture sachets, proper recovery was obtained using C18 SPE. The assessment of greenness of the proposed protocol guaranteed the superiority of the presented method. Safer sorbents and chemicals are favored for use in routine extraction of nutraceuticals., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Rebamipide (REB) is quinolinone derivative compound, which is used for the treatment of stomach ulcers., Objective: The development of four spectrophotometric methods for quantification of REB and its impurity and degradation product: the debenzoylated isomer of REB (DER)., Methods: Method A is ratio difference spectrophotometry where 254 and 291 nm were selected for REB and 320 and 355 nm were selected for DER, allowing spectral discrimination for both. Method B is derivative ratio spectrophotometry, where the peak amplitudes of the first derivative of ratio spectra at 261 and 350.2 nm for REB and DER, respectively, are determined. Method C is a second derivative approach, which allows quantification of both REB and DER at 337 and 340 nm, respectively. Method D is mean centering of ratio spectra, where electronic absorption spectra of REB and DER were recorded and divided by a suitable divisor from DER and REB, respectively, and then the mean center is represented by the ratio spectrum so obtained., Results: The proposed methods are simple, selective, and sensitive in the quantification of REB and DER. These methods were validated according to International Conference on Harmonization guidelines. Statistical analyses performed on the findings from the suggested methods and those obtained from reported methods revealed high accuracy and good precision., Conclusion: The developed and validated methods are useful for quality control assay in routine analyses., Highlights: First derivative, second derivative, derivative ratio, and mean centering methods for quantification of REM and DER. These methods are useful for analysis of REB in pharmaceutical dosage form., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Diflunisal (DIF) has analgesic and anti-inflammatory activity. It is a pharmacopeial drug found in the British Pharmacopoeia (BP), and its major pharmacopeial impurity is biphenyl-4-ol (BPL)., Objective: DIF has not previously been determined together with BPL. The presence of BPL could significantly affect the dose of DIF in its dosage forms; hence it is crucial to determine DIF and BPL in each other's presence., Methods: TLC is the first proposed method, where DIF and BPL were separated on silica gel TLC F254 plates. The eluent was toluene-acetone-acetic acid solution (3.5:6.5:1, v/v). Reversed-phase (RP) HPLC is the second suggested method, where a mixture of DIF and BPL was separated on a C18 (5 µm ps, 250 mm and 4.6 id) column using phosphate buffer pH 4 (0.05 M)-acetonitrile (40:60, v/v). Detection was carried out at 254 nm in both methods., Results: For the TLC method, concentration ranges of 0.5-3 and 0.3-1.7 µg/band were used, with mean percentage recoveries of 100.22% (SD 0.893) and 100.52% (SD 0.952) for DIF and BPL, respectively. The RP-HPLC method was carried out over a concentration range of 5-30 and 2-9 μg/mL, with mean percentage recoveries of 100.10% (SD 1.259) and 98.88% (SD 0.822) for DIF and BPL, respectively., Conclusion: The TLC and RP-HPLC methods were successfully applied for the determination of DIF and BPL, quantitatively, whether in bulk powder or in pharmaceutical formulations., Highlights: Two chromatographic methods were developed and validated according to International Council on Harmonization guidelines for the assay of DIF and its pharmacopeial impurity., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The demand for natural fungicides to replace synthetic ones has surged since toxic residues persist in soils, causing environmental contamination and posing a serious threat to worldwide public health. In the context of crop protection and enhancing the efficiency and safety of fungicides, nanotechnology is an eco-friendly strategy in managing fungal pathogens. In the present study, essential oils were isolated from the peels of four citrus fruits ( Citrus lemon , Citrus aurantifolia , Citrus maxima , and Citrus sinensis ) and were investigated using gas chromatography-mass spectrometric analysis. Monoterpene hydrocarbon was the most predominant group and limonene was the most abundant in the four oils. The antifungal potential of the oils was investigated, and the most active oil ( Citrus lemon ) was loaded into hexosomal dispersion, and its antifungal potential was retested against the same fungi. The structurally unique nano-based formulation showed great potency for fungal control. To the best of our knowledge, it is the first time the oil of Citrus lemon in nano-hexosomes has been formulated and its fungicidal activity examined. The data collected suggest that citrus essential oils (CEOs), especially when nano-formulated, could be successfully used in integrated fungus management programs.

A gradient elution high-performance liquid chromatographic method with a diode array detector is introduced for the first time for the simultaneous estimation of three drugs, namely, oxytetracycline hydrochloride (OXT), lidocaine (LDC), and bromhexine hydrochloride (BRH), in a veterinary formulation (OxyClear® solution) that contains many interfering additives. The method used a C-8 column. The chromatographic eluting solution included acidified water (0.1% trifluoroacetic acid in water) and acetonitrile at a 1-ml/min flow rate and 254 nm as a nominated detection wavelength. The chromatographic process was assessed in terms of linearity, precision, accuracy, LOD, and LOQ. OXT, LDC, and BRH were linear in the range of 1-60, 5-100, and 1-60 μg/ml, respectively. The three drugs were determined successfully without the interference of three excipients having UV absorbances. Furthermore, the purities of the peaks of the three drugs were confirmed by comparing the UV spectra of investigated peaks to the UV reference spectra in Clarke's Analysis of Drugs and Poisons. The greenness value of the method was 0.69 with a faint green-colored pictogram using the AGREE tool. These merits recommend the application of the planned method in QC laboratories for purity testing and concentration assays for the pure drugs and commercial formulations., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

The assessment of greenness of analytical protocols is of great importance now to preserve the environment. Some studies have analyzed either only the neurotransmitters, dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA), together or with other neurotransmitters and biomarkers. However, these methods have not been investigated for their greenness and were not compared with each other to find the optimum one. Therefore, this study aims to compare seven published chromatographic methods that analyzed the four neurotransmitters and their mixtures using the National Environmental Method Index, Analytical Eco-Scale Assessment (ESA), and Green Analytical Procedure Index (GAPI). As these methods cover both qualitative and quantitative aspects, they offer better transparency. Overall, GAPI showed maximum greenness throughout the analysis. Method 6 was proven to be the method of choice for analyzing the mixture, owing to its greenness, according to NEMI, ESA, and GAPI. Additionally, method 6 has a wide scope of application (13 components can be analyzed), high sensitivity (low LOQ values), and fast analysis (low retention times, especially for glutamate and GABA).

A promising Cordia myxa fruit (CMF) extract targets an additional incorporation in functional foods. It retains appropriate health welfares owing to its antioxidant properties with limited incorporation in food matrices due its hydrophobicity. Therefore, CMF extract micro- and nanocapsulation was performed to protect and facilitate consistency of produced hydrophobic foods matrices. Furthermore, to determine its phytochemicals, antioxidant, and cytotoxic effects by applying analytical HPLC, FRAP and SRB assay, respectively. HPLC analysis of the tested extracts revealed the presence of, 25.59 ± 1.78 mg catechin/g, 69.68 ± 4.20 mg quercetin/g, and 112.72 ± 8.38 mg gallic acid/g extract. The CMF extract displayed a potent DPPH radicals' scavenger and FRAP high reduction capability in a dose-dependent manner. The potent pharmacological activities of CMF extract may be ascribed to high concentration of polyphenolics including flavonoids which strongly reported to possess an antitumor and antioxidant activities. To confirm the efficient CMF incorporation in micro- and nanosystems and their thermal stabilities to withstand the high temperatures applied during some food processing. DSC of the apparent melt of non-capsulated CMF and encapsulated forms (MCMF and NCMF) in sodium alginate gel and beads was studied. Results showed that melting point of CMF extract (86.17 °C) indicating its inability whereas the MCMF and NCMF melting points (226.45 and 383.87 °C, respectively) demonstrating the capability of expending alginate - packaging material to shield the vital active compounds of C. myxa fruit to be applied in different targeted delivery products especially that disclosed to high thermal treatments., Competing Interests: 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., (© 2021 The Author(s).)