Polymeric Nanoparticles and Nanodiamond-Based Quantum Sensing: Applications in Managing Metabolic-Associated Diseases with a Natural Extract as a Therapeutic Agent

Type 2 diabetes mellitus (T2DM) is a growing epidemic, projected to affect around 700 million people worldwide by 2045. Obesity is a risk factor for developing insulin resistance and T2DM, with a significant number of cases linked to weight gain. Despite various treatments for T2DM and obesity, their limited efficacy and side effects drive the search for better alternatives, including medicinal plants. However, these often face challenges like low stability and bioavailability. Studies on triterpenes from Eucalyptus tereticornis leaves, named OBE100, show that triterpenes can reverse metabolic abnormalities, reducing body weight, proinflammatory cytokines, and liver lipotoxicity, additionally modulating the expression of lipogenic and gluconeogenic genes in diet induced obesity mouse models. OBE100, a mix of ursolic acid (UA), oleanolic acid (OA), ursolic acid lactone (UAL), and other minor components, is more effective than its individual components. This thesis reports the first encapsulation of OBE100 using oral polymeric nanocarriers, which protect it from degradation and improve solubility and bioavailability. The hypothesized mechanism involves free radical generation, antioxidant capacity, and anti-inflammatory activity. This thesis explores this action mechanism using nanodiamond-based quantum sensing in combination with physiological and molecular methods for in vitro testing in hepatic cells and ex vivo, using precision-cut mouse liver slices as liver disease models. The results of this work are presented in the following six chapters of this thesis. Chapter 1 presents this thesis's general overview, problem statement, justification, theoretical framework, hypothesis, and objectives. Chapter 2 presents the development of an oral nanocarrier encapsulating OBE100 triterpene-rich extract, the physicochemical characterization, and the results in the evaluation of the metabolic effect in a diet-induced obesity mouse model reducing body weight, hyperglycemia, and insulin resistance, additionally modulating the expression of lipogenic and gluconeogenic genes. The results confirm/demonstrate/suggest OBE100 as an alternative for treating obesity and some of its metabolic complications. Chapter 3 details quantum sensing results with fluorescent nanodiamonds (FNDs) to elucidate OBE100's antioxidant action mechanism in HepG2 cells as a metabolic associate steatotic liver disease (MASLD) model. FNDs, coated with a specific antibody, measured cytosolic and mitochondrial free radicals. OBE100 reduced lipid accumulation and enhanced cellular respiration, ATP production, and oxidative stress response. Quantum sensing revealed the mechanism of OBE100 at the subcellular level, supporting its use in predicting free radical generation in metabolic liver diseases. Chapter 4 evaluates the antioxidant effect of OBE100 in fresh and steatotic mice liver tissue using nanodiamond-based quantum sensing to test antioxidant drugs in precision-cut liver slices. It demonstrates the impact of lipid accumulation in the liver by increasing free radicals associated with steatosis and how OBE100 reduced free radicals without affecting tissue viability, showing its antioxidant activity and potential use as a therapeutic agent in liver diseases. Chapter 5 includes a general discussion and conclusions, the main findings of this study, and suggestions for future research directions. Chapter 6 lists the publications and scientific activities pursued in developing this doctoral thesis and related collaborative projects.

• Autores: Escobar Chaves, Elkin Leandro
• Tipo de recurso: Doctoral thesis
• Fecha de publicación: 2024
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/47911
• Acceso en línea: https://hdl.handle.net/10495/47911
• Palabra clave: Enfermedades Metabólicas; Metabolic Diseases; Obesidad; Obesity; https://id.nlm.nih.gov/mesh/D009765; Diabetes Mellitus Tipo 2; Diabetes Mellitus, Type 2; Nanopartículas; Nanoparticles; Quantum sensing; Type 2 diabetes; https://id.nlm.nih.gov/mesh/D008659; https://id.nlm.nih.gov/mesh/D003924; ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-sa/4.0/