Abstract

Obesity-associated metabolic disorders, including insulin resistance, type 2 diabetes mellitus, cardiovascular 
disease, and non-alcoholic fatty liver disease, are driven in large part by chronic low-grade inflammation. 
Conventional anti-inflammatory therapies often suffer from poor tissue specificity, limited bioavailability, and 
systemic side effects, which constrain their long-term clinical utility. Smart nanoparticles have emerged as 
advanced drug delivery platforms capable of precise, controlled, and stimuli-responsive delivery of anti
inflammatory agents to diseased metabolic tissues. These nanoparticles are engineered to sense pathological 
microenvironmental cues such as pH, oxidative stress, enzymatic activity, or inflammatory mediators, enabling 
site-specific drug release. This review provides a comprehensive overview of smart nanoparticle systems 
designed for the precision delivery of anti-inflammatory agents in obesity-associated metabolic disorders. We 
discuss the inflammatory mechanisms linking obesity to metabolic dysfunction, key design principles of smart 
nanoparticles, and current therapeutic strategies targeting adipose tissue, liver, and immune cells. Critical 
challenges related to safety, scalability, and clinical translation are examined, and emerging opportunities for 
next-generation nanomedicine approaches are highlighted. Collectively, smart nanoparticles represent a 
promising avenue for improving the efficacy and safety of anti-inflammatory therapies in metabolic disease 
management.