Abstract

Obesity is characterized by chronic low-grade inflammation that plays a central role in the development of 
insulin resistance, type 2 diabetes, cardiovascular disease, and other components of metabolic syndrome. This 
inflammatory milieu is driven largely by dysfunctional white adipose tissue, immune cell infiltration, and 
sustained production of pro-inflammatory mediators. Conventional pharmacological interventions often fail to 
adequately target inflamed tissues and are associated with systemic side effects, reduced efficacy, and poor 
patient adherence. In this context, inflammation-responsive nanomaterials have emerged as a promising 
strategy for controlled, site-specific drug delivery in obesity-related chronic inflammatory states. These smart 
nanomaterials are engineered to respond to inflammatory cues such as acidic pH, elevated reactive oxygen 
species, proteolytic enzymes, and inflammatory cytokines, enabling precise and on-demand drug release at 
diseased sites. This review provides a comprehensive overview of the pathophysiological basis of obesity
associated inflammation, principles of inflammation-responsive nanomaterial design, and key nanotechnological 
platforms developed for controlled drug release. We discuss current preclinical evidence supporting their 
therapeutic potential, address major translational challenges, and highlight future perspectives for integrating 
inflammation-responsive nanomedicine into metabolic disease management. Harnessing inflammation
triggered drug delivery systems may represent a paradigm shift toward safer, more effective, and personalized 
therapies for obesity-related chronic inflammatory disorders.