N-(2′-Hydroxyphenyl)-2-propylpentanamide (OH-VPA) is a valproic acid (VPA) derivative with improved antiproliferative activity toward breast cancer (MCF-7, MDA-MB-231, and SKBr3) and human cervical cancer cell lines (HeLa) compared to that of VPA. However, the pharmacological mechanism of OH-VPA activity remains unknown. High-mobility group box 1 (HMGB1) is an important enzyme that is highly expressed in tumor cells and has a subcellular localization that is dependent on its acetylation or oxidative state. Therefore, in this study, we analyzed changes in HMGB1 sub-cellular localization and reactive oxygen species (ROS) as well as changes in HeLa cell viability in response to treatment with various concentrations of OH-VPA. This compound is formed by the covalent bond coupling VPA to a phenol group, which is capable of acting as a free radical scavenger due to its chemical similarities to quercetin. Our results show that OH-VPA induces nuclear to cytoplasmic translocation of HMGB1, as demonstrated by confocal microscopy observations and infrared spectra that revealed high quantities of acetylated HMGB1 in HeLa cells. Cells treated with 0.8 mM OH-VA exhibited decreased viability and increased ROS levels compared with the lower OH-VPA concentrations tested. Therefore, the antiproliferative mechanism of OH-VPA may be related to histone deacetylase (HDAC) inhibition, as is the case for VPA, which promotes high HMBG1 acetylation, which alters its subcellular localization. In addition, OH-VPA generates an imbalance in cellular ROS levels due to its biochemical activity.
Aim: New approaches are required to improve compliance in older patients with problems in swallowing traditional formulations. A novel memantine orodispersible tablet (ODT) was formulated, and its bioavailability and taste acceptability were evaluated. Materials & methods: In vitro characterization of ODT comprised dispersion in simulated saliva prior to dissolution assay in a limited volume of biorelevant media. A single oral dose of 20-mg memantine ODT exhibits similar bioavailability to that of an immediate release 20-mg tablet in a healthy population under fasting conditions. Results: 90% confidence interval for Cmax was of 96.78–106.52% and 98.27–104.78% for AUC0–72. An applied palatability survey showed exceptional acceptance of the formulation. Conclusion: Memantine microspheres prepared by a solid-dispersion technique results in ODT with adequate biopharmaceutical performance.
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