Turkish journal of pharmaceutical sciences最新文献

Objectives: Glioblastoma (GB) is the most aggressive type of brain tumor in adults, and the chemical agent temozolomide (TMZ) is widely used for its treatment. However, TMZ resistance can lead to therapeutic failure. The aim of this study was to investigate the effect of the bioflavonoid fisetin on GB cell growth and on overcoming TMZ resistance in TMZ-sensitive, inherited-resistant, and acquired-resistant GB cells the effect of fisetin on TMZ efficacy evaluin primary GB cells.

Materials and methods: GB cell lines (T98G; intrinsic TMZ-resistant, A172; TMZ-sensitive, A172-R; acquired TMZ-resistant) and primary GB cells derived from patient samples were treated with effective doses of TMZ (ranging from 900 to 1000 μM), fisetin (ranging from 13.78 to 16.40 μM), or a combination of both. TMZ resistance was acquired in A172 cells through stepwise increases in TMZ concentration. Real-time cell proliferation was measured using the xCELLigence system. The migratory capacity of the cells was evaluated using a wound-healing assay. The RNA expression of the epithelial-to-mesenchymal transition (EMT)-inducing transcription factor E-box-binding homeobox 1 (ZEB1) was assessed by quantitative polymerase chain reaction. Cell assays were analyzed by analysis of variance, and ZEB1 expression was analyzed by t-test.

Results: Fisetin substantially enhanced the effect of TMZ in all the cell lines included in the present study, as evidenced by significant decreases in cell proliferation and wound-healing, and in ZEB1 expression (p<0.0001). In addition, TMZ+fisetin reduced ZEB1 expression in primary GB tumors but not in butterfly GB cells.

Conclusion: Fisetin alone was effective against GB; importantly, the TMZ+fisetin combination demonstrated greater efficacy than TMZ alone by enhancing sensitivity to TMZ through downregulation of ZEB1 in various resistant models, including patient-derived samples. Since ZEB1 is associated with EMT and drug resistance, fisetin may be a promising anticancer candidate to improve chemotherapeutic efficacy in resistant GB and to shed light on personalized treatments, pending further preclinical research.

Objectives: 5-hydroxymethylfurfural (5-HMF) derivatives, found in many natural products, exhibit various biological activities. Benzoate derivatives enhance cellular re-epithelialization without inducing cytotoxicity. This study aimed to evaluate the wound-healing potential of six benzoate derivatives of 5-HMF by usingan in vitro cell culture method.

Materials and methods: Six ester derivatives of 5-HMF were synthesized, and the molecular structures were elucidated by proton-1 nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and Quadrupole time-of-flight mass spectrometry. The effects of the compounds on neuronal and fibroblast cell survival were determined in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The total oxidation state (TOS) and total antioxidant capacity (TAC) were measured spectrophotometrically. The effects of the lead compounds (M3 and M5) on fibroblast migratory potential were evaluated using a wound-healing scratch assay.

Results: The MTT test showed that M2, M3, M5, and M6 did not damage fibroblasts at any tested concentration (10^-1 μM-10^-2 μM). M3 and M5 increased fibroblast cell numbers at all tested concentrations (p≤0.05 to p≤0.001). It was observed that M2, M3, M5, and M6 at concentrations of 10^-1 μM and 1 μM did not damage the neuronal cells. Also, M3 and M5 did not damage neuronal cells at 10 μM. M3 and M5 exhibited lower oxidant activity (p≤0.001) than other compounds in TOS tests, and showed higher antioxidant activity than other compounds in TAC tests. In the scratch test, the wound area in the M3 group was 72% on the first day and decreased to 32% on the second day (p≤0.001). On the other hand, in the M5 group, the wound area was 81% on the first day and decreased to 25% on the second day (p≤0.001).

Conclusion: M3 and M5 promote cell migration and have the highest potential for wound healing among the compounds tested.

Objectives: Vaginal nanofibers with high surface area and tunable porosity are a promising platform for vaginal administration. Poly(vinyl alcohol) (PVA) is a widely used polymer in the pharmaceutical field due to its hydrophilic, biodegradable, non-toxic, and mucoadhesive properties. This study aimed to optimize PVA-based electrospun nanofibers for vaginal drug delivery by evaluating polymer concentration, solvent system, and collector rotation speed using a design of experiments-based approach.

Materials and methods: PVA was dissolved in distilled water (DW) at 90 °C to prepare polymer solutions; then N, N-dimethylformamide (DMF) or ethanol was added. The surface tension, viscosity, and conductivity of the polymer solutions were evaluated. For the production of nanofibers via electrospinning, the parameters selected were PVA concentrations of 7.5% and 15%, collector rotation speed of 100 and 1000 rpm, and two solvent systems (DMF: DW and ethanol: DW). Mechanical and mucoadhesive properties of nanofibers were evaluated using a texture analyzer.

Results: Viscosity and conductivity increased as polymer concentration increased. An increase in PVA concentration resulted in increased tensile strength of the nanofibers, from 1.41±0.07 to 3.92±0.14 MPa (p<0.0001). Nanofiber diameters ranged from 196±41 nm to 1721±114 nm (p<0.0001). All formulations exhibited complete wettability with contact angles of 0°. Ex vivo mucoadhesion studies revealed that collector rotation speed influenced the work of adhesion, with the highest mucoadhesion observed for the R3 formulation produced at 1000 rpm.

Conclusion: The solvent system and collector rotation speed were found to influence the morphological structure of the fibers. R3 (7.5% PVA, ethanol/DW, 1000 rpm) formulation was found to be more suitable than other formulations based on its mechanical and mucoadhesive properties. It was concluded that in the production of PVA nanofibers, the rotating speed of the collector, the polymer concentration, and the solvent system directly affect the mechanical and mucoadhesive properties of the nanofibers.

Objectives: Vaccination is a cornerstone of public health, and maintaining the vaccine cold chain within a temperature range of 2-8 °C is essential to preserve vaccine efficacy and prevent wastage. Community pharmacists are highly accessible healthcare professionals who play a crucial role in vaccine supply, storage, and public education. The aim of this study was to qualitatively assess vaccination and cold-chain practices in community pharmacies within Türkiye's primary healthcare system.

Materials and methods: A qualitative study was conducted with 15 community pharmacists in Ankara, Türkiye, using semi-structured face-to-face interviews carried out between September 15 and 30, 2024. Participants were recruited through snowball sampling until thematic saturation was achieved. All interviews were audio-recorded, transcribed verbatim, and analyzed using Braun and Clarke's seven-phase thematic analysis. Data management was performed using ATLAS.ti version 24.0, and reporting adhered to the COREQ checklist.

Results: Three main themes emerged: vaccination practices, vaccine logistics and cold-chain management, and vaccine hesitancy. Pharmacists reported frequent patient inquiries, particularly regarding influenza, human papillomavirus, and childhood vaccines. Participants demonstrated a high level of awareness of cold-chain protocols, including the use of dedicated refrigerators and continuous temperature monitoring systems. Vaccine hesitancy, especially toward Coronavirus Disease 2019 vaccines, was primarily attributed to misinformation, with pharmacists emphasizing the importance of evidence-based and empathetic communication.

Conclusion: Community pharmacists possess substantial technical knowledge in vaccine logistics and play a critical role in patient counseling. Strengthening regulatory frameworks, professional training, and communication skills may further enhance pharmacists' contributions to immunization efforts and vaccine confidence.

Objectives: The objective of this study was to develop a simple, precise, and accurate high-performance thin-layer chromatographic (HPTLC) method for the simultaneous estimation of dapagliflozin (DAP) and vildagliptin (VIL) in a combined pharmaceutical formulation. Managing diabetes often involves using a combination of drugs to better control blood sugar levels. One such effective formulation is combination of DAP, an SGLT2 inhibitor, with VIL, a DPP-4 inhibitor, in a single formulation. To ensure the quality and consistency of these combination products, it is important to have a simple and reliable method for analyzing both drugs simultaneously.

Materials and methods: An aluminium-backed pre-coated silica gel 60 F₂₅₄ TLC plate was employed as the stationary phase. The mobile phase consisted of toluene, methanol, and ethyl acetate in a volumetric ratio of 5:3:2. Prior to plate development, the chamber was saturated with the mobile phase for 20 minutes. Detection was carried out at 210 nm, selected based on the isosbestic point of the analytes.

Results: The developed method successfully separated the analytes with retardation factor values of 0.57±0.02 for DAP and 0.26±0.02 for VIL. The method exhibited linearity in the concentration ranges of 0.6 to 1.4 μg per band for DAP, with a correlation coefficient (r²) of 0.997 and 6 to 14 μg per band for VIL, with an r² of 0.998. The limit of detection was found to be 0.02 μg/band for DAP and 0.19 μg/band for VIL. Similarly, the limit of quantification was determined to be 0.07 μg/band for DAP and 0.58 μg/band for VIL.

Conclusion: The proposed HPTLC method allows for the simultaneous estimation of DAP and VIL with high accuracy, precision, and sensitivity. Owing to its satisfactory analytical performance, the method is suitable for routine quality control of combined dosage forms containing DAP and VIL.

Objectives: Comprehensive Medication Management (CMM) is pivotal in optimizing clinical outcomes through personalized medication review and patient engagement. Patient satisfaction surveys, such as the Medication Management Patient Satisfaction Survey (MMPSS), play a crucial role in assessing the quality of these services. However, there is currently no Turkish version of the MMPSS available. This study aimed to translate, culturally adapt, and validate the Turkish version of the MMPSS to assess patient satisfaction with CMM services provided by pharmacists in Türkiye.

Materials and methods: Following established guidelines for cross-cultural instrument validation, the MMPSS was translated into Turkish and culturally adapted. The survey underwent forward translation, expert panel review, back-translation, and pilot testing. Data collection occurred in a tertiary care university hospital between September 9, 2022, and March 21, 2023. Psychometric analyses included reliability testing (Cronbach's alpha), factorial validity using confirmatory factor analysis, and test-retest reliability using the Intraclass Correlation Coefficient (ICC).

Results: A total of 124 participants (82.7%) completed the survey. Participants were mostly women (57.3%) and elderly, with a mean age of 70.43 years, three comorbidities, and six medications. The Turkish MMPSS demonstrated excellent internal consistency (Cronbach's α = 0.858) and test-retest reliability (ICC=0.937), confirming its reliability over time. Factor analysis supported a one-factor structure, consistent with the original MMPSS framework, and all items showed strong correlations.

Conclusion: The Turkish version of the MMPSS is a reliable and valid instrument for assessing patient satisfaction with CMM services in Türkiye. Its implementation can enhance the evaluation and improvement of clinical pharmacy services, ultimately promoting better patient care and outcomes.

Objectives: Pharmacoeconomics is an important branch of science that should be taken into account by countries' social security institutions in order to rationally manage drug expenditures within healthcare budgets for the aging population. Pharmacists trained in pharmacoeconomics make a great contribution to this field. This study aims to draw attention to the inclusion of pharmacoeconomics education as a compulsory course in the curricula of pharmacy faculties in Türkiye.

Materials and methods: Fifty-one pharmacy faculties in Türkiye were analysed. The pharmacoeconomics courses and their contents in the curriculum of these faculties were evaluated. The course contents, European Credit Transfer System and credits, weekly and meeting hours of the faculties offering pharmacoeconomics courses were analyzed.

Results: There are 51 pharmacy faculties in Türkiye. Of these pharmacy faculties, 33 are operating under state universities and 18 under foundation universities. There is no pharmacoeconomics course in the curriculum of 82.35% of the pharmacy faculties (n=42). In the other 17.65% (n=9) of the faculties, there is a pharmacoeconomics course in the curriculum. The course contents of the faculties are similar, and basic pharmacoeconomics information is generally given. There are no faculty members who have completed their PhDs in this field.

Conclusion: This study, the first to systematically evaluate the situation in all pharmacy faculties in Türkiye, has revealed that pharmacoeconomics education is limited. Making pharmacoeconomics courses mandatory in the curriculum of pharmacy faculties is necessary to comply with international standards and enable pharmacists to contribute more effectively to rational drug use and the sustainability of healthcare systems.

Objectives: Antimicrobial resistance is a major problem in the treatment of infectious diseases. Therefore, it is important to develop new and effective antimicrobial agents. For this purpose, a new series of compounds with a 2,4-dihydro-3H-1,2,4-triazole-3-thione structure was synthesized.

Materials and methods: 2,4-dihydro-3H-1,2,4-triazole-3-thione compounds (T1-T8) were synthesized by heating thiosemicarbazide derivatives under alkaline conditions. Infrared (IR), ¹H-NMR, and ¹³C-NMR spectroscopic methods were used to elucidate the chemical structures of the compounds. The antimicrobial activity of the compounds against eight bacterial strains (five Gram-negative and three Gram-positive) and two fungal strains was evaluated using the microdilution method.

Results: Compounds T4, carrying a benzoyl group, and T6, carrying a phenethyl group, showed the best antibacterial activity against Enterococcus faecalis ATCC 29212, with minimum inhibitory concentrations (MICs) of 41.79 mg/L and 81.25 mg/L, respectively. Compound T6 also demonstrated the strongest antibacterial activity against Staphylococcus epidermidis ATCC 12228, with an MIC of 40.62 mg/L. Antifungal activity assays revealed that compounds T4, T6, and T8 were the most potent against Candida albicans ATCC 90028, with MIC values of 40.62-83.59 mg/L, and that T6, T7, and T8 were the most potent against Candida glabrata ATCC 90030, with MIC values of 40.62-162.5 mg/L.

Conclusion: Among the compounds, T6 appears to exhibit significant antimicrobial activity against both Gram-positive bacteria (e.g., E. faecalis ATCC 29212 and S. epidermidis ATCC 12228) and fungi (e.g., Candida strains).

Objectives: Comorbid psychiatric disorders, especially depression, pose challenges in epilepsy. Antiepileptic drugs, including levetiracetam, can also have psychiatric adverse effects, necessitating strategies to address mood regulation. The study aims to assess the impact of melatonin administration on depressive behavior in epileptic and non-epileptic mice.

Materials and methods: Male albino mice were assigned to different treatment groups. Levetiracetam (20 mg/kg ip) was injected for 14 days; melatonin (25 mg/kg ip) was injected for 7 days. Additional groups were included for epileptic mice. Maximal electroshock was used to induce seizures: locomotor activity, immobility time in the forced swimming test (FST), latency, and food consumption were measured in the novelty-suppressed feeding test (NSFT).

Results: There were insignificant differences in locomotor activity between groups. In the FST, levetiracetam administration significantly increased the immobility duration compared to the control group in epileptic and non-epileptic mice (p<0.05). The immobility duration in the levetiracetammelatonin groups of both epileptic and non-epileptic mice significantly decreased compared to the levetiracetam alone group (p<0.01). In NSFT, the levetiracetam group exhibited a significantly longer latency (p<0.01) and less food intake (p<0.05) compared to the control group; these changes were reversed when levetiracetam-melatonin was administered. In epileptic groups, the difference in latency was insignificant, while food consumption increased significantly (p<0.05) in the levetiracetam-melatonin group compared to the levetiracetam-alone group. The results observed with melatonin were similar to those of imipramine.

Conclusion: Melatonin was found to reduce depressive behavior in both non-epileptic and epileptic groups. These results suggest that melatonin could be a potential therapeutic agent for countering the depressive effects of levetiracetam.

Objectives: This study aims to enhance the bioavailability and polymorphic stability of Ticagrelor, a metastable, low-soluble and low-permeable Biopharmaceutics Classification System Class IV drug, by exploring different formulation approaches.

Materials and methods: Ticagrelor was taken as a model drug for the enhancement of bioavailability and polymorphic stability. Initially, various techniques, such as micronization, amorphous solid dispersion (ASD), and Self-Microemulsifying Drug Delivery System, were evaluated for dissolution enhancement. Based on the improvement in dissolution rate, polymorphic stability, and process viability, an ASD technique was selected for dissolution enhancement of Ticagrelor. Co-povidone VA 64 and vitamin E TPGS were used as carriers for the preparation of Ticagrelor solid dispersion (SD) by the solvent evaporation technique. The formulation was optimized and further evaluated for dissolution performance in biorelevant media fasted state simulated gastric fluid and fasted state simulated intestinal fluid. The bioavailability of the Ticagrelor SD tablet formulation was compared with a conventional immediate release tablet formulation prepared by wet granulation process in line with reference product Brilinta^® (AstraZeneca LP). In vivo pharmacokinetic (PK) studies were carried out in Wistar rats with due approval from ethics committees such as CPCSEA and IAEC (CPCSEA/DIPS/02/23/61). Patients are not involved in this study, hence informed consent not applicable.

Results: The relative bioavailability and peak plasma concentration (C_max) of Ticagrelor SD formulation compared to conventional immediate release tablet formulation in line with Brilinta^® (AstraZeneca LP) were found to be 141.61±2.29% and 137.0±0.59%, respectively. Further, based on a doseadjusted PKs study of Ticagrelor SD, a 70 mg Ticagrelor tablet formulated with the SD technique was found to be equivalent to a 90 mg dose of Ticagrelor conventional immediate release tablet formulation with a comparable C_max, area under the curve (AUC)_0-24, and AUC_0-∞. Visual observation of the dissected gastric organ through a stereomicroscope revealed no redness or bleeding post-administration of Ticagrelor SD formulations.

Conclusion: The SD technique with carrier co-povidone VA 64 and vitamin E TPGS prepared by the solvent evaporation process could yield a Ticagrelor formulation with improved bioavailability and polymorphic stability.