Turkish Journal of Pharmaceutical Sciences最新文献

Objectives: Interferons (IFNs) are one of the most important components of innate immunity against viruses, especially those carrying the RNA genomes such as influenza viruses. Upon viral infection, the IFNs are rapidly secreted, inducing the expression of several genes in the target cells and establishing an antiviral state. In this study, the effects of proteins encoded by some IFN-related genes on influenza A virus RNA-dependent RNA polymerase enzyme were investigated. We evaluated the importance of these proteins in the pathogenesis of different influenza A virus types.

Materials and methods: The IFN-related genes were amplified by polymerase chain reaction from the HEK293 cDNA library and cloned into pCHA expression vector. The expression of genes and subcellular localizations of the proteins were determined by Western blotting and immunofluorescence staining, respectively. The effects of IFNs-related proteins on virus RdRP enzyme were determined by influenza A virus mini-replicons.

Results: The study revealed that the influenza A virus infections significantly altered the transcript level of the IFN-related CCL5, IFIT1, IFIT3, IFITM3, and OAS1 genes in HEK293 cells. It was determined that the alteration of the gene expression was also related to the virus type. The mini-replicon assays showed that the transient expression of CCL5, IFI27, OAS1, IFITM3, IFIT1, and IFIT3 have inhibitory effects on WSN and/or DkPen type virus RdRP enzymes. We observed that the proteins except OAS1 inhibited WSN type RdRP enzyme at a higher level than that of DkPen enzyme.

Conclusion: It was concluded that influenza A virus infection significantly alters the IFN-related gene expression in the cells. Most of the proteins encoded from these genes showed an inhibitory effect on the virus RdRP enzymes in the HEK293 cells. The inhibition of the influenza virus RdRP with IFN-related proteins may be the result of direct or indirect interactions between the host proteins and the viral enzyme subunits.

Objectives: The aim of the investigation was to prepare sustained release (SR) pellets of diltiazem hydrochloride employing almond gum and gelucire. The study was performed to explore the suitability of almond gum in the preparation of pellets of diltiazem hydrochloride without the use of microcrystalline cellulose and role and effectiveness of hydrophobic gelucire (43/01) in controlling the drug release.

Materials and methods: Pellets were prepared by extrusion-spheronization of the blend previously obtained by incorporation of the drug in a mixture of melted gelucire 43/01 and almond gum. A 3² factorial design was employed to study the effect of two independent variables, almond gum and gelucire, on the size, friability and drug release from pellets. Scanning electron microscopy, differential scanning calorimetry and infrared spectroscopy were performed to characterize pellets.

Results: Free flowing spherical pellets could be prepared. The 3² factorial study revealed that as the proportion of almond gum increased, the size of pellets increased, while increasing gelucire had opposite effect. The yield of pellets prepared in different formulations is in the range of 86 to 92%. The size of the pellets varied from 1128 to 1458 μ. Higher amounts of gelucire resulted in pellets with greater friability, whereas increasing the amount of almond gum yielded pellets with low friability. The pellets exhibited SR of diltiazem and the presence of gelucire in the matrix of the pellets had an enhanced sustaining effect on release.

Conclusion: Dispersion of the drug in gelucire before it was converted to pellets resulted in extended release of drug. The drug release rate changed with changes in the proportion of pellet composition. The results of the study suggest that employing gelucire (43/01) in the preparation of pellets is a useful approach in the design of SR products of highly water-soluble drug such as diltiazem hydrochloride.

Objectives: Cancer diseases have been linked to a huge number of causes that led to deaths in this century along with cardiovascular and lung diseases. Most death-leading types of cancer are colon, lung, breast, and prostate cancers. Due to the remarkable properties of gold (Au) nanocarrier, they are used to deliver and improve tamoxifen (Tam) citrate activity in Caco-2 and MCF-7 cells.

Materials and methods: In this study, preparation of Au nanoparticles (NPs), zeta-potential and size, high resolution transient electron microscopy (HRTEM), high-performance liquid chromatography, ultraviolet-visible spectra, fluorescence microscopy, fourier infrared spectroscopy, and real-time cellular analysis xCELLigence technology were investigated.

Results: The zeta-average size of the Tam- β-cyclodextrin (β-CD)-hyaluronic acid (HA)-chitosan (Chi)-Au nanocomposite is 82.02 nm with a negative zeta potential of -23.6. Furthermore, HRTEM images showed that, successful formulation of polymer shell around Au core and the Au NP shape is mostly spherical, triangle and irregular. Furthermore, the fluorescence microscope image showed proper cellular uptake of the Tam-β-CD-HA-Chi-Au nanocomposite in MCF-7 and Caco-2 cells. Additionally, Tam-β-CD-HA-Chi-Au nanocomposite significantly improved the cytotoxic activity of Tam citrate on Caco-2 cells. IC₅₀ value of Tam reduced from 8.55 µM to 5.32 µM, after 48 h of incubation time (p value <0.00001).

Conclusion: This study showed that Tam-β-CD-HA-Chi-Au nanocomposite is a potential nanocarrier for delivering the drug to Caco-2 and MCF-7 cancer cells, since it has improved Tam citrate activity on colorectal cancer cells. After all, the developed formula showed more effect on Caco-2 than MCF-7. The prepared nanocomposite could be used to improve the cancer therapy in clinical trials.

Objectives: The "safe if natural" perception of herbal products may have several undesirable side effects. It is important to raise awareness in public order to change this perception and ensure safer use of herbal products. The role of pharmacists is to supply herbal medicines safely and to provide accurate information to the patients about herbal products. The aim of this study was to analyze the perspective, knowledge, attitude, and behavior of community pharmacists about phytovigilance.

Materials and methods: A cross-sectional analysis was performed using community pharmacists (n= 879) using face-to-face surveys between April-June 2019 in Istanbul. For statistical analysis, student's t-test and one-way ANOVA were used to compare the mean values of the groups.

Results: It was determined that 58.1% of the pharmacists heard phytovigilance for the first time and 93.5% of them had not reported any safety-related herbal medicine reported so far. Among the reasons for not reporting, well-known adverse reactions were found to be 24.2% and the difficulty of reporting was found to be 21.8%. 84.6% of pharmacists have never received training related to phytovigilance. It was found that pharmacists with a working experience of more than 20 years primarily selected herbal products provided in their pharmacy based on the manufacturing company primarily, whereas others selected based on the efficacy of the products.

Conclusion: The results of this study have revealed the necessity to increase training on the safety of herbal medicines to cover all stakeholders and to give due importance to phytovigilance. The phytovigilance systems established in some countries for public health should be expanded to other countries. There is a need for a more user-friendly reporting system to increase adverse reaction reporting by pharmacists and other healthcare professionals. In the future, plan to perform studies to raise awareness in the public and promote reporting with digital technologies.

Parkinson's disease (PD) is a type of movement disorder that affects the ability to perform daily activities. It is considered that 1 million people in the U.S. and more than 10 million people worldwide live with PD. It is a chronic and progressive disease, so symptoms worsen over the time. Patients experience motor symptoms such as tremors, stiffness and slow motion, and non-motor symptoms such as sleep problems, constipation, anxiety, depression and fatigue. Dopaminergic drugs are critical for treating motor symptoms in PD. Levodopa (L-DOPA) is the "gold standard" medication for the control of motor symptoms. Because of the progression of the disease, the effectiveness of oral L-DOPA decreases over time and motor fluctuations such as "delayed ON", "no ON" and unpredictable "ON-OFF" periods appear. These motor fluctuations affect the quality of life of the patient at a high rate and the patient has problems in fulfilling his daily morning routines. Gastrointestinal (GI) problems, as the common non-motor symptom, are the most important cause of motor fluctuations that occur because of inadequate oral treatment with the progression of PD. When oral treatments are not sufficient, non-oral treatments that are not affected by GI problems are required. In this review, the treatment strategies, developed and approved non-oral drug delivery systems in the early and advanced stages of PD are emphasized.

Objectives: Passiflora incarnata L., commonly called folk medicine declaredly used for an enormous range of therapeutic purposes, one such is antioxidant potency. The study prioritized to determine the phytochemical analysis of total phenolics, flavonoids, alkaloids, and tannins contents as well as the antioxidant properties through 1,1-diphenyl-2-picrylhydrazyl (DPPH) quenching assay, 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) cation decolorization test, superoxide, and hydrogen peroxide radical scavenging assays of ethanol extract of P. incarnata leaves.

Materials and methods: The organoleptic characteristics such as color, odor, appearance, taste, and other characters such as drying range and fiber contents were analyzed as preliminary data. Analytical parameters like total phenolic content, total tannins, total alkaloid content, and total flavonoid with multiple antiradical scavenging activity (DPPH, ABTS, superoxide and H₂O₂ scavenging assays) with IC₅₀ (μg/mL) in terms of inhibition percentage with various concentrations of the ethanolic extract studied.

Results: P. incarnata possessed a high radical scavenging activity with a phenolic content of 2.48 mg gallic acid equivalent/g of extract in leaves, whereas the total flavonoid content was 2.1, respectively.

Conclusion: High antioxidant activity was noticed in P. incarnata extract, in which might be of higher levels of flavonoids and phenols. Findings in the studies revealed that P. incarnata is a veritable source for antioxidant drug bioprospecting in scientific research and pharmaceutical industries.

Objectives: In this study, we report the quality control results of drug-related impurity analysis of seven raw materials of ciprofloxacin hydrochloride marketed in Algeria.

Materials and methods: According to the European Pharmacopoeia (Eur. Ph.), high-performance liquid chromatography (HPLC) was used to analyze (B, C, D and E) impurities, while thin layer chromatography (TLC) used to control impurity A.

Results: HPLC analysis showed that the C1, C2, C3, C4, and C6 samples have individual contents of specified impurities (B, C, D, E), unspecified and the total of all present impurities conform to norms. The C5 sample contains a very high content (0.579%) of impurity C, which is a photodegradation product and the impurities total (0.625%) exceeding limit, while C7 sample has a slightly higher content (0.118%) of unspecified impurity. The control solution of impurity A was not migrated in all developed TLC plates, so the system is not compliant, for this reason, an HPLC analysis protocol was developed.

Conclusion: The results showed that impurity A content conformed in all samples except for the C6 sample, which has equal content to the limit. Therefore, we recommend revising the detecting technique of impurity A by TLC in the Eur. Ph. or replacing it with a more sensitive technique such as HPLC.

Objectives: Gemini surfactant nanocurcumin (Gemini-Cur) is a novel formulation of Curcumin (Cur) with dramatic suppressive effects on cancer cells. Here, we investigated the cancer effects of Gemini-Cur in a human gastric adenocarcinoma cell-line (AGS) through the evaluation of the expression of long non-coding RNAs colon cancer-associated transcript-2 (CCAT2) and its downstream c-Myc as known oncogenic modulators of tumorigenesis.

Materials and methods: The AGS cells were treated with Gemini-Cur and pure Cur in a time- and dose-dependent manner. The toxicity of Gemini-Cur was studied using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and scratch tests. Furthermore, real-time polymerase chain reaction and Western blotting techniques were employed to evaluate the expression of genes.

Results: Gemini-Cur significantly affected the viability of AGS cells in a dose- and time-dependent manner with inhibitory concentration 50 values of 59.32, 40.88, and 19.63 µM during 24, 48, and 72 h, respectively. Our findings showed that Gemini-Cur effectively decreased the expression levels of lnc-CCAT2 and c-Myc genes. Western blotting analysis also confirmed the down-regulation of c-Myc in treated samples compared to controls.

Conclusion: Gemini-Cur attenuates the proliferation of AGS cells partly through modulation of the lncCCAT2-related pathway.