Epigenomics is the study of the gene expression changes due to epigenetic processes and not due to the deoxyribonucleic acid (DNA) base sequence alterations. The key mechanisms of epigenetic regulation include DNA methylation, histone modifications, and noncoding RNAs. Epigenetic alterations in cancer are predominantly linked with hypermethylation of promoters of the tumor suppressor genes, global DNA hypomethylation, and increased expression of histone deacetylases (HDAC). There is a growing need to investigate epigenetic patterns and to provide safe and effective, innovative therapeutic strategies for oncology patients, who did not improve on traditional anticancer regimens. The epi-drugs (e.g., DNA methyltransferase inhibitors, e.g., azacitidine and decitabine and HDAC inhibitors, e.g., vorinostat and romidepsin) have been approved for the clinical use. In this paper, we provide a brief overview of the mechanisms of action and targets for novel epi-drugs, focusing on their potential clinical applications in patients with solid tumors, resistant to standard oncology treatments.
Metastatic cancer, especially in the growing population of geriatric patients, presents a big challenge to these patients, as well as to treatment teams and the entire health care system. This article describes some common medical problems faced by patients with metastases to liver and bone, and...
Compounding formulations, including semi-solid medication forms, must meet criteria related to specific stability and quality, during a period of their use. In suspension-type ointments, one of the criteria for assessment of their correct manufacturing is particle size, which in the compounding preparation cannot exceed 90 µm. An appropriate level of particle disintegration can be achieved via a selection of technological parameters and qualitatively compatible excipients. In this study, benzocaine ointments were prepared using a levigation process. The time of its application on the particle size of API in suspension ointments was evaluated. In parallel, the effect of mixing parameters and the co-solvent used on the precipitation of active substance crystals in emulsion ointments during the storage of these formulations for 28 days was investigated. Forty suspension and emulsion ointments were prepared using selected ointment bases: Pentravan®, Lekobaza, Lekobaza LUX, Eucerin Ointment I, Nourivan™ Antiox, Fitalite™, containing 2% benzocaine. Based on the results of the stability test, four formulations were selected to study the release kinetics of benzocaine in vitro. These formulations were characterized by the rate of release consistent with the Higuchi model, and the fastest rate of release occurred from the Eucerin-based emulsion ointment.
Background and aim: Managing the therapy of patients with chronic liver diseases and comorbidities presents significant challenges for physicians and pharmacists, particularly regarding drug-induced liver damage and polypharmacy. Given the liver’s central role in drug detoxification, polypharmacy in liver disease requires special attention. The aim of the review was to assess the prevalence of polypharmacy among patients with chronic liver diseases. Approach and Results: A literature search focused on randomized controlled trials, database reviews, and medical records. Review of PubMed, SCOPUS, and ScienceDirect databases identified 2578 manuscripts, however only 11 studies met the inclusion criteria. The results of studies showed that the prevalence of polypharmacy among patients with chronic liver disease can exceed 50%, and can lead to high prevalence of MRP and pDDI among those patients. Conclusions: Findings reveal a critical link between polypharmacy and adverse outcomes in chronic liver diseases, including cirrhosis, hepatitis, and non-alcoholic fatty liver disease. Individualized treatment plans, considering factors such as age, gender, comorbidities, and liver disease severity are essential. The interventions focused on mitigating MRP and reducing pDDI need to be implemented in order to reduce the potential harm of polypharmacy.
Growth hormone (somatotropin—STH) deficiency therapy requires daily injections of recombinant human growth hormone. The FDA approved treatment with STH with one dose per week for the first time in 2021. However, injectable drug application is accompanied by numerous inconveniences. Therefore, an attempt was made to formulate a less invasive STH formulation for topical application to the skin. A substrate was prepared based on a polymer, methylcellulose (MC), into which STH was introduced at a concentration of 1 mg/g. Simultaneously, formulations were made with STH, to which albumin (ALB) was added at different concentrations: 0.1%, 0.2% and 0.5%. A test of the degree of STH permeation was carried out, as well as the effect of ALB on STH permeation parameters. Selected rheological properties of the formulations obtained were investigated. A test of STH permeation in simulated in vivo conditions through porcine skin indicated a relatively good bioavailability of over 80% and confirmed the effectiveness of MC as a carrier for growth hormone. ALB prolonged the STH penetration rate and increased the penetration degree of STH to 93%. The hydrogels obtained were found to be typical shear-thinning, thixotropic fluids.