Biochemical, ameliorative and cytotoxic effects of newly synthesized curcumin microemulsions: Evidence from in vitro and in vivo studies

Curcumin is known to exhibit antioxidant and tissue-healing properties and has recently attracted the attention of the biomedical community for potential use in advanced therapies. This work reports the formulation and characterization of oil-in-water F127 microemulsions to enhance the bioavailability of curcumin Microemulsions showed a high encapsulation efficiency and prolonged release. To investigate the interactions of curcumin with one unit of the polymeric chain of surfactant F127, ethyl butyrate, and sodium octanoate, as well as the interaction between ethyl butyrate and one unit of the F127 polymer chain, the Density Functional Theory (DFT) calculations at the M06-2X level of theory, were performed in water solution. The MTT assay was used to assess the cytotoxicity of free and encapsulated curcumin on non-malignant and malignant cell lines. Combination effects were calculated according to Chou-Talalay’s principles. Results of in vitro studies indicated that MCF7 and HepG2 cells were more sensitive to curcumin microemulsions. Moreover, a synergistic relationship was observed between curcumin microemulsions and cisplatin in all affected fractions of MCF7 and HepG2 cells (CI < 0.9). For in vivo investigation, thioacetamide-intoxicated rats received thioacetamide (100 mg/kg Sc) followed by curcumin microemulsions (30 mg/kg Ip). Thioacetamideintoxicated rats showed elevated serum liver enzymes, blood urea nitrogen (BUN), and creatinine levels, and a significant reduction in liver superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). Curcumin microemulsions reduced liver enzymes and serum creatinine and increased the activity of antioxidant enzymes in thioacetamide-treated rats in comparison to the untreated thioacetamide-intoxicated group. Histopathological investigations confirmed the biochemical findings. Overall, the current results showed the desirable hepatoprotective, nephroprotective, and anti-cancer effects of curcumin microemulsions

Pluronic F127/Doxorubicin microemulsions: Preparation, characterization, and toxicity evaluations

The development of drug delivery systems minimizing the side effects of conventional chemotherapy is one of the major challenges in the field of biomaterials for cancer treatment. This work reports the formulation and characterization of oil-in-water Pluronic F127 microemulsions to enhance the bioavailability of doxorubicin (DOX). The density functional theory (DFT) calculations at the M06-2X level of theory were done to study the interaction details of DOX with ethyl butyrate, sodium caprylate, and one unit of the polymeric chain of surfactant Pluronic F127 in water solution, which are used in the synthesis process. Specifically, the quantum theory of atoms in molecules (QTAIM) analysis was performed to determine the nature of interactions. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were calculated to show the direction of charge transfer within each complex. Furthermore, the natural bond orbital (NBO) analysis was performed on the studied systems. The size of F127/DOX microemulsion was about 7.0 nm by dynamic light scattering analysis. In vitro toxicity of standard DOX and DOX-loaded microemulsions were assessed against MCF-7 and C152 (malignant) and HUVEC (non-malignant) cell lines. Intracellular lactate dehydrogenase (LDH) leakage was evaluated as an indicator of membrane integrity. In vitro assessments revealed that Pluronic F127/DOX microemulsions caused substantial morphological changes and greater cytotoxic effects than standard DOX. Pluronic F127/DOX microemulsions were injected intraperitoneally at 12 and 24 mg/kg into rats. The free (bulk) DOX group induced severe histopathological changes and significant increases in serum kidney markers and serum liver enzymes. The 24 mg/kg dose of Pluronic F127/DOX microemulsions also induced fatty changes and elevation of serum liver enzymes and creatinine. Overall, this new drug delivery system formulation shows promise for cancer treatment and deserves to be further studied in the future

Decoding clinical biomarker space of COVID-19:exploring matrix factorization-based feature selection methods

Abstract One of the most critical challenges in managing complex diseases like COVID-19 is to establish an intelligent triage system that can optimize the clinical decision-making at the time of a global pandemic. The clinical presentation and patients’ characteristics are usually utilized to identify those patients who need more critical care. However, the clinical evidence shows an unmet need to determine more accurate and optimal clinical biomarkers to triage patients under a condition like the COVID-19 crisis. Here we have presented a machine learning approach to find a group of clinical indicators from the blood tests of a set of COVID-19 patients that are predictive of poor prognosis and morbidity. Our approach consists of two interconnected schemes: Feature Selection and Prognosis Classification. The former is based on different Matrix Factorization (MF)-based methods, and the latter is performed using Random Forest algorithm. Our model reveals that Arterial Blood Gas (ABG) O₂ Saturation and C-Reactive Protein (CRP) are the most important clinical biomarkers determining the poor prognosis in these patients. Our approach paves the path of building quantitative and optimized clinical management systems for COVID-19 and similar diseases