Development and optimization of fluoxetine orally disintegrating tablets using Box-Behnken design

Purpose: To develop and optimise some variables that influence fluoxetine orally disintegrating tablets (ODTs) formulation.Methods: Fluoxetine ODTs tablets were prepared using direct compression method. Three-factor, 3- level Box-Behnken design was used to optimize and develop fluoxetine ODT formulation. The design suggested 15 formulations of different lubricant concentration (X1), lubricant mixing time (X2), and compression force (X3) and then their effect was monitored on tablet weight (Y1), thickness (Y2), hardness (Y3), % friability (Y4), and disintegration time (Y5).Results: All powder blends showed acceptable flow properties, ranging from good to excellent. The disintegration time (Y5) was affected directly by lubricant concentration (X1). Lubricant mixing time (X2) had a direct effect on tablet thickness (Y2) and hardness (Y3), while compression force (X3) had a direct impact on tablet hardness (Y3), % friability (Y4) and disintegration time (Y5). Accordingly, Box-Behnken design suggested an optimized formula of 0.86 mg (X1), 15.3 min (X2), and 10.6 KN (X3). Finally, the prediction error percentage responses of Y1, Y2, Y3, Y4, and Y5 were 0.31, 0.52, 2.13, 3.92 and 3.75 %, respectively. Formula 4 and 8 achieved 90 % of drug release within the first 5 min of dissolution test.Conclusion: Fluoxetine ODT formulation has been developed and optimized successfully using Box- Behnken design and has also been manufactured efficiently using direct compression technique.Keywords: Box-Behnken experimental design, Orally disintegrating tablets, Direct compression, Antidepressant, Magnesium stearate, Mixing tim

Potential bioactivity of Phoenix dactylifera fruits, leaves, and seeds against prostate and pancreatic cancer cells

The use of functional foods’ phytochemicals in the chemoprevention of different cancer diseases has become one of the hot scientific areas in the clinical nutrition field. For instance, the Khalas palm cultivar (KPC; Phoenix dactylifera) is one of the natural sustainable resources that have high bioactivity and functionality. This study aimed to investigate the antiproliferative activity and mode of action of KPC’s different parts on prostate (Pc3) and pancreatic (panc1) cancer cells at a molecular level. In the methods, KPC’s leaves, seeds, and fruits’ chemical composition and phytochemical analysis were analyzed. Also, the cytotoxic effects of each extract were assessed against pc3 and panc1 cell lines. Besides, induction of apoptosis, cell cycle analysis, and gene expression of both Cap3 and Cap9 were studied. The obtained results indicated that KPC leaves extract exhibited the highest significant (P < 0.01) anti-proliferation activity against the utilized cancer cell lines compared to fruits and seeds extracts. Also, there were significant (P < 0.05) differences in the phenolic contents, flavonoid of compounds, and antioxidant power of the leaves when compared to the seeds and fruits. Additionally, the highest cytotoxic effect (lowest IC50) was recorded with leave extract than seeds and fruits. Meanwhile, the seeds extract induced (P < 0.05) the apoptosis and arrested cells in the G2/M phase as well as up-regulated the gene expression of the apoptotic-related genes (Casp3 and Casp9) compared to the control group. In conclusion, this study showed that the presence of bioactive components in the KPC different parts extracts have the significant ability to induce the apoptotic pathway that could down-regulate the proliferation of prostate (pc3) and pancreatic (panc1) cancer cells. The pathway mechanism of action was induced by the phytol molecule presented in its leaves extract

The mechanism of action of Spirulina as antidiabetic: a narrative review

Spirulina happens to be a special type of blue-green algae that originally emerged 3.5 billion years ago and was used as a source of nutrition. Spirulina gets its name from the filaments’ spiral or helical structure, but its true name is taxonomically Genus Arthrospira which encompasses several species. The most common species are S. fusiformis, S. maxima, and S. platensis. It is rich in various nutrients and chemical components including protein, carbohydrates, lipids, vitamins, minerals, pigments, chlorophyll, and enzymes. Spirulina’s active molecules and rich nutrients make it have several pharmacological activities and uses including antioxidant, anti-inflammatory, immunomodulatory, immune system booster, anticancer, antiviral activity, and neuroprotective properties. It is also utilized as a nutritional supplement and for weight loss. Moreover, several studies confirm that Spirulina improves insulin sensitivity and reduces blood glucose levels in rat models as well as diabetic patients. The reason behind this unique behavior could be credited to the presence of several active components in it, but the action’s fundamental mechanism is still a matter of debate. Several studies have suggested different mechanisms including anti-inflammatory activity, increased insulin sensitivity, inhibition of gluconeogenesis, antioxidant activity, modulating gut microbiota composition, improved glucose homeostasis, and insulin receptor activation. Therefore, it became clear that Spirulina is a mine of active substances used as a nutritional supplement and reduces blood glucose levels or used in conjunction with other treatments to tackle type 2 diabetes. Further exploration is required to fully explain its effects on human physiology and determine optimal dosages for treatment

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Signaling Pathway Inhibitors, miRNA, and Nanocarrier-Based Pharmacotherapeutics for the Treatment of Lung Cancer: A Review

Lung cancer is one of the most commonly diagnosed cancers and is responsible for a large number of deaths worldwide. The pathogenic mechanism of lung cancer is complex and multifactorial in origin. Thus, various signaling pathways as targets for therapy are being examined, and many new drugs are in the pipeline. However, both conventional and target-based drugs have been reported to present significant adverse effects, and both types of drugs can affect the clinical outcome in addition to patient quality of life. Recently, miRNA has been identified as a promising target for lung cancer treatment. Therefore, miRNA mimics, oncomiRs, or miRNA suppressors have been developed and studied for possible anticancer effects. However, these miRNAs also suffer from the limitations of low stability, biodegradation, thermal instability, and other issues. Thus, nanocarrier-based drug delivery for the chemotherapeutic drug delivery in addition to miRNA-based systems have been developed so that existing limitations can be resolved, and enhanced therapeutic outcomes can be achieved. Thus, this review discusses lung cancer’s molecular mechanism, currently approved drugs, and their adverse effects. We also discuss miRNA biosynthesis and pathogenetic role, highlight pre-clinical and clinical evidence for use of miRNA in cancer therapy, and discussed limitations of this therapy. Furthermore, nanocarrier-based drug delivery systems to deliver chemotherapeutic drugs and miRNAs are described in detail. In brief, the present review describes the mechanism and up-to-date possible therapeutic approaches for lung cancer treatment and emphasizes future prospects to bring these novel approaches from bench to bedside

Protective effects of two Astragalus species on ulcerative colitis in rats

WOS: 000386952600014Purpose: To investigate the anti-inflammatory activities of root extracts of Astragalus gummifera and Astragalus kurdicus, as well as their protective effects against acetic acid-induced ulcerative colitis (UC) in rats. Methods: The roots of both species were shade-dried, pulverized to fine powder and extracted with 80 % ethanol. The extracts were lyophilized using freeze-dryer, and their anti-inflammatory effects were evaluated in rats by carrageenan-induced paw edema. In UC study, the extracts, at doses of 200 and 400 mg/kg, were given orally to rats for 5 days, with the last dose given 2 h prior to colitis induction. Histopathological studies were carried out on the colon tissues. Dexamethasone (DEX) was used as standard anti-inflammatory drug. Results: A. gummifera (400 mg/kg) and A. kurdicus (200 and 400 mg/kg) significantly reduced carrageenan-induced edema, offered protection against UC and arrested UC-induced increases in myeloperoxidase (MPO) activity. Histological examination of colon sections also revealed evidence of extract-induced protection from UC. Conclusion: These results suggest that A. gummifera and A. kurdicus root extracts have promising potential as sources of anti-inflammatory agents which may be useful in the treatment of UC

PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer

Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models

Synthesis and Evaluation of Novel <i>S</i>-alkyl Phthalimide- and <i>S</i>-benzyl-oxadiazole-quinoline Hybrids as Inhibitors of Monoamine Oxidase and Acetylcholinesterase

New S-alkyl phthalimide 5a–f and S-benzyl 6a–d analogs of 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazole-2-thiol (4) were prepared by reacting 4 with N-bromoalkylphthalimide and CF3-substituted benzyl bromides in excellent yields. Spectroscopic techniques were employed to elucidate the structures of the synthesized molecules. The inhibition activity of newly synthesized molecules toward MAO-A, MAO-B, and AChE enzymes, was also assessed. All these compounds showed activity in the submicromolar range against all enzymes. Compounds 5a and 5f were found to be the most potent compounds against MAO-A (IC50 = 0.91 ± 0.15 nM) and MAO-B (IC50 = 0.84 ± 0.06 nM), while compound 5c showed the most efficient acetylcholinesterase inhibition (IC50 = 1.02± 0.65 μM). Docking predictions disclosed the docking poses of the synthesized molecules with all enzymes and demonstrated the outstanding potency of compounds 5a, 5f, and 5c (docking scores = −11.6, −15.3, and −14.0 kcal/mol against MAO-A, MAO-B, and AChE, respectively). These newly synthesized analogs act as up-and-coming candidates for the creation of safer curative use against Alzheimer’s illness

Ambroxol hydrochloride loaded gastro-retentive nanosuspension gels potentiate anticancer activity in lung cancer (A549) cells

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRG(K)) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect