KIU Publications

Herbal anti-obesity agents provide multi-target modulation of appetite signaling, adipose inflammation, lipid handling, insulin sensitivity, and gut–brain–liver axis communication. However, their translation into reliable therapies is limited by poor aqueous solubility, chemical instability, extensive first-pass metabolism, efflux transport, and variability in botanical composition and microbiome-driven biotransformation. Smart nanodelivery systems aim to overcome these constraints by combining nanoencapsulation with controlled or stimuli-responsive release, improved mucosal residence, and redesigned biodistribution. By stabilizing exposure and aligning release kinetics with pathway-level objectives, these systems can support metabolic reprogramming rather than transient symptomatic effects. Mechanistically, sustained delivery can dampen adipose inflammatory signaling, normalize lipolysis, suppress pathological adipogenesis, improve hepatic lipid metabolism, and promote thermogenic and mitochondrial programs, while gut-targeted release can reshape microbiota-derived metabolites and bile acid signaling that influence energy balance. Smart designs include pH- and enzyme-responsive matrices for region-specific intestinal release, redox-responsive systems for intracellular payload liberation, and composite carriers that enable sequential or co-delivery of complementary phytochemicals. Yet obesity is a chronic-use indication; therefore, long-term safety, manufacturability, reproducible characterization, and clear PK–PD linkage to clinically meaningful endpoints remain decisive. This review evaluates smart nanodelivery strategies for herbal anti-obesity agents, emphasizing controlled release as a driver of durable metabolic reprogramming and outlining translational challenges and development priorities.