Annales pharmaceutiques francaises最新文献

Objectives: The primary objective was to develop and validate four novel UV/visible spectrophotometric methods for the quantification of tafamidis meglumine in bulk drug, proprietary capsules, and spiked urine samples, ensuring accuracy, sensitivity, and environmental sustainability for pharmaceutical analysis.

Methods: Four spectrophotometric approaches were established using absorbance and area under the curve (AUC) measurements, employing both zero-order and first-order derivative techniques. Method validation followed ICH guidelines, assessing linearity, accuracy, precision, sensitivity (LOD, LOQ), and greenness. Methanol was used as a green solvent, and eco-friendliness was evaluated using AGREE and ComplexGAPI metrics.

Results: All methods exhibited excellent linearity (R²=0.9980-0.9995) over a 3-18μg/mL range. Accuracy was confirmed with recovery rates between 99.00% and 100.57%. Precision studies yielded %RSD values below 2%, indicating high reproducibility. Sensitivity was demonstrated with LOD and LOQ values from 0.27μg/mL to 2.3μg/mL. The use of methanol minimized environmental impact, and high AGREE and ComplexGAPI scores validated the methods' eco-friendly nature.

Conclusion: The developed spectrophotometric methods are simple, rapid, sensitive, and environmentally sustainable for quantifying tafamidis meglumine in various matrices. These validated approaches set a new standard for green analytical chemistry in pharmaceutical quality control, ensuring both regulatory compliance and reduced environmental footprint.

Objectives: Glioblastoma (GBM) is one of the most aggressive and treatment-resistant types of brain cancer, and conventional therapies such as surgery, chemotherapy, and radiotherapy have limited effectiveness in controlling it. In this context, the use of natural compounds with anticancer properties has been explored as a complementary strategy. The purpose of the current study was to assess the cytotoxic and pro-apoptotic potential of the plant extracts Echium amoenum and Valeriana officinalis in U87-MG glioblastoma cells.

Materials and methods: The Maceration technique was used to prepare the plant extracts. U87-MG cells and L-929 cell lines were cultured and treated with various concentrations (31.25, 62.5, 125, 250, 500 and 1000μg/mL) of the extracts upon reaching optimal confluence. An MTT assay was performed to evaluate the cytotoxicity at 24, 48 and 72hours. To investigate the expression of apoptosis-related genes (Bax, Bcl-2 and Caspase-3, Caspase-9 and puma), RNA was extracted and converted to cDNA and then the expression of these genes was analyzed by real-time PCR.

Results: MTT assay results showed that both extracts inhibited cancer cell growth in a dose- and time-dependent manner. At 72hours and a concentration of 1000μg/mL, E. amoenum extract exhibited the highest inhibition rate (96%), while V. officinalis extract showed 95% inhibition under the same conditions. At the molecular level, E. amoenum extract significantly upregulated Caspase-3 expression by more than 20-fold (P<0.0001) indicating a strong activation of the apoptotic pathway, while V. officinalis extract did not cause a significant change in the expression of this gene. Additionally, Bcl-2 expression was significantly elevated in the E. amoenum-treated group (P<0.001). However, the upregulation of Bcl-2-a gene associated with cell survival-was considerably weaker compared to the robust induction of Caspase-3. Also, E. amoenum significantly upregulated Caspase-9 expression (P<0.0001), indicating activation of the intrinsic apoptotic pathway.

Conclusion: The results demonstrated that extracts from V. officinalis and E. amoenum have anticancer effects on U87-MG cells, possibly through the induction of apoptosis. E. amoenum was more effective in raising Caspase-3 and initiating pathways leading to programmed cell death, whereas V. officinalis did not change the expression levels of apoptotic genes. Our finding suggests that this plant may exert its anticancer effects through non-apoptotic or alternative apoptotic mechanisms, rather than the classical intrinsic or mitochondrial pathway. These findings imply that more research should be done on the application of natural substances as a supplemental approach to GBM therapy.

Objectives: The objective of this study was to assess whether implementing a protocol could improve adherence to European guidelines on postoperative antithrombotic therapy prescription in patients undergoing coronary artery bypass-grafts surgery (CABG) after acute coronary syndrome (ACS).

Methods: We included patients who underwent cardiac surgery between January 2018 and December 2022. The population was divided in two groups, one before (group 1) and one after (group 2) the dissemination of a protocol on postoperative antithrombotic therapy issued by a multidisciplinary collaboration (January 2021) and its subsequent implementation during ward rounds. We analysed the protocol's impact on adherence to European guidelines in terms of antithrombotic therapy at discharge.

Results: We included 259 patients, 83.8% were men and the median age was 67 [58; 74] years. At baseline, group 1 (n=152) and group 2 (n=107) had similar demographic characteristics except for smoking status and ACS events. Patients in group 2 had a higher rate of guideline adherence in terms of postoperative antithrombotic therapy (group 1=58.6% vs. group 2=82.2%, P<0.001). Using logistic regression accounting for demographic and temporal factors, the effect of the intervention was positive but not statistically significant. Adherence increased significantly over time, suggesting that the intervention contributed to an overall trend of improved adherence as apart of ongoing quality improvement efforts.

Conclusion: Implementing the protocol was associated with a positive effect on guideline adherence for postoperative antithrombotic therapy in ACS patients undergoing CABG. Although the intervention's independent effect was not statistically significant after adjustment, the findings support its role in achieving sustained improvement in adherence over time.

Cancer remains a major global health challenge, characterized by low survival rates and significant side effects from conventional treatments. The metal-organic frameworks (MOFs) offer distinctive features that make them highly suitable for medical innovations. This study presents the development of MOFs as nanocarriers for the anticancer drug axitinib (AXT) to address these issues. Specifically, the MOFs were composed of titanium isopropoxide as metal ions and terephthalic acid as ligands, synthesized via a hydrothermal approach. The pH-responsive Ti-MOF was designed to enhance targeted drug delivery and minimize AXT side effects. The Ti-MOF was analyzed through various techniques, including UV-Vis spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy coupled with Energy Dispersive X-ray (SEM-EDX), zeta potential analysis, particle size measurement, Raman spectroscopy, and thermo gravimetric analysis (TGA). In vitro drug release studies at 37°C demonstrated that these porous carriers significantly slowed the release of AXT under neutral conditions, with only 4.5% to 8.0% released, mimicking normal tissue environments. In contrast, under acidic conditions (i.e., at pH 5), which simulates the acidic conditions of cancerous tissues, the release of AXT increased substantially, reaching 76% to 78% after 12h, While staying low at 8.0% to 9.5% at pH 7.4, this pH-sensitive release pattern results from the increased dissolution of the MOF material in acidic environments. This characteristic makes it a promising approach for targeted cancer therapy. The design of these MOF-based nanocarriers underscores their potential to enhance the precision and effectiveness of anticancer treatments.

Proteolysis-targeting chimera (PROTAC) molecules are hetero-bifunctional chemical entities with three different units which include a ligand that binds to a protein of interest; a second ligand that binds to the E3 ubiquitin ligase; and a linker that conjugates the two ligands together. The technology utilizes the ubiquitin-proteasome system (UPS) to target a specific protein and induce its degradation in the cell. PROTAC has drawn the interest of researchers in anti-cancer drug discovery and has yielded a better outcome in degrading regulatory proteins, kinases, nuclear receptors, transcription factors, and enzymes. This paper discusses this technology and its application to COVID-19 drug discovery. In 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), an infectious agent emerged from Wuhan resulting in millions of deaths worldwide. The WHO declared it a global pandemic because of its fast transmissibility and infectivity across the continents. To curtail this menace, efforts were made to develop therapeutics and inhibitors very quickly. Vaccines and therapeutics discovery were fast-tracked, and already FDA-approved drug molecules were also repurposed - many of which were protein inhibitors. However, PROTAC technology potentially offers a more direct and sustainable contribution to anti-COVID drug discovery than protein inhibition-based therapeutics.

This work presents a comprehensive study of the crystal structure, spectral properties (IR and UV-Vis), thermal behavior, and antimicrobial activity of homopiperazinium dichromate (C₅H1₄N₂)Cr₂O₇(VI). X-ray diffraction reveals that the compound crystallizes in the monoclinic space group P2₁/c, with unit cell dimensions a=8.7275(8)Å, b=10.5769(11)Å, and c=14.7467(10)Å and β=122.941(4)°. The crystal packing is stabilized by intermolecular N-H…O and C-H…O hydrogen bonds, with Hirshfeld surface analysis revealing dominant O…H/H…O interactions contributing 80.5% to the overall crystal cohesion. UV-Vis absorption bands are observed at 279, 354, and 446nm, with an estimated band gap energy of 3.019eV, indicating high stability and moderate optical activity. Thermal analysis shows an intense endothermic fusion peak followed by continuous decomposition, leading to chromium oxide formation. Antimicrobial tests demonstrate significant inhibition activity against tested pathogens, including notable antifungal effects against Candida albicans. These results highlight the potential of this hybrid material in antimicrobial development and photochemical applications.