Abstract

Obesity profoundly alters insulin pharmacokinetics and pharmacodynamics through expanded and inflamed 
adipose depots, altered subcutaneous tissue architecture, and systemic low-grade inflammation, all of which 
complicate insulin replacement therapy. Nanoparticle (NP)-based delivery systems offer multiple tools to 
address these barriers: protection of insulin from degradation, controlled and targeted release, glucose
responsive dosing, and alternative non-injectable routes (oral, inhaled, transdermal). This review summarizes 
how obesity changes insulin absorption and action, surveys NP platforms (lipid, polymeric, inorganic, hybrid) 
and administration routes, assesses glucose-responsive and adipose-targeting strategies, and examines 
preclinical and clinical progress. We highlight translational challenges safety, immunogenicity, scale-up, and 
regulatory pathways, and propose a roadmap for development that prioritizes patient acceptability, rigorous 
obesity-relevant models, and biomarker-driven clinical trials. Nanoparticle approaches show promise to improve 
glycaemic control and adherence in people with obesity-associated diabetes, but success will require coordinated 
advances in design, testing in obesity-specific physiologies, and early engagement with regulators. 
Keywords: insulin delivery, nanoparticles, obesity, glucose-responsive, oral insulin