Injectable Therapies and their Effects on the Modulation of Chronic Inflammation in Immunometabolic Diseases: Obesity, Cancer, and Type 2 Diabetes Mellitus

Low-grade chronic inflammation (LGCI) is a central etiological factor and a persistent driver in the pathogenesis of non-communicable chronic diseases (NCCDs), notably obesity, cancer, and type 2 diabetes mellitus (T2DM) [1, 2]. This expanded and in-depth review proposes and critically analyzes an integrated and innovative therapeutic strategy, focusing on injectable administration, which combines agents with complementary and synergistic mechanisms of action: Dimethyl Sulfoxide (DMSO), Coenzyme Q10 (CoQ10), Alpha-Lipoic Acid (ALA), Curcumin, Resveratrol (RSV), Glutathione (GSH), and microRNA-146a mimetics (miR-146a) [3]. The choice of the injectable route of administration (intravenous, intramuscular, or subcutaneous) is justified by the need to optimize the systemic bioavailability and tissue targeting of these compounds, overcoming the severe limitations of absorption and first-pass metabolism of the oral route, especially for lipophilic nutraceuticals and oligonucleotides [4, 5]. The main focus of the approach lies in the modulation of the immunometabolic axis, with emphasis on restoring the negative feedback of miR-146a on the IRAK1/TRAF6/NF-κB signaling pathway, a molecular circuit crucial for immunological and metabolic homeostasis [6, 7]. Additionally, the article delves into the role of resveratrol in activating sirtuins (SIRT1) and modulating leptin and insulin resistance, comparing this multidimensional approach with current gold-standard therapies (e.g., GLP-1/GIP agonists). It is hypothesized that this synergy of agents, supported by nanomedicine for the efficient delivery of miR-146a mimetics, can modulate LGCI more comprehensively, optimize mitochondrial function and biogenesis, and restore central and peripheral metabolic balance. The critical analysis of safety and clinical evidence, notably for intravenous DMSO and miRNA mimetics, is an essential component of this review, positioning this approach as a potential new frontier in the treatment of these chronic immunometabolic diseases [8, 9].