Inducing Macrophage Polarization Using Metformin-Encapsulated Nanostructured Lipid Carriers to Combat Obesity and T2DM: A Research Protocol

Introduction: Obesity and type 2 diabetes mellitus (T2DM) are driven by chronic inflammation in white adipose tissue, characterized by an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. This disruption contributes to insulin resistance and metabolic dysfunction. Metformin, a widely used antidiabetic drug, has demonstrated potential in promoting M2 polarization and inhibiting M1 polarization. This protocol explores an innovative therapeutic approach using Metformin encapsulated in nanostructured lipid carriers (NLCs) to enhance its efficacy. Methods: Male C57BL/6J mice will be fed a high-fat diet (HFD) to induce obesity and treated with streptozotocin (STZ) to simulate T2DM conditions. The mice will receive daily or weekly doses of Metformin, either via oral gavage or encapsulated in NLCs, over 12 weeks. Key assessments will include glucose tolerance tests (GTT), intraperitoneal insulin tolerance tests (IPITT), body weight monitoring, and insulin and cytokine profiling through ELISA. Adipose tissue will be analyzed post-euthanasia using histological techniques, flow cytometry, and quantitative PCR to evaluate macrophage polarization. Results: The NLC-encapsulated Metformin is anticipated to demonstrate improved therapeutic efficacy by reducing fasting blood glucose levels, body weight, and pro-inflammatory cytokines while increasing anti-inflammatory cytokines compared to traditional oral Metformin administration. This is attributed to NLCs' targeted delivery, enhanced bioavailability, and sustained drug release. Discussion: This study aims to establish the superiority of NLC-encapsulated Metformin in mitigating metabolic dysfunction and inflammation compared to traditional methods. The results could underscore the importance of targeted therapies for treating obesity and T2DM and pave the way for translational clinical applications. Conclusion: Findings from this study may advance the development of targeted therapies for metabolic diseases, providing a foundation for future clinical applications in managing obesity and T2DM.