Oral nanoparticles (NPs) are more suitable for obesity control compared to NPs administered intravenously, as their convenience increases patient compliance. Herein, we developed an oral nano-system to improve the anti-obesity efficacy of celastrol (Cel). The observed enhanced efficacy was mediated by zein core NPs decorated with adipose-homing peptides that were coated with N-trimethylated chitosan. The optimized Cel/AHP-NPs@TMC exhibited spherical morphology by TEM, as well as narrow size distribution (221.76 ± 6.73 nm) and adequate stability in a gastrointestinal environment. Based on the combined delivery advantages of AHP-NPs@TMC - i.e., improved cellular internalization within Caco-2 cells and enhanced white adipose tissue (WAT) vascular targeting - Cel/AHP-NPs@TMC significantly reduced the body weight, blood lipid levels, adipose inflammation, and WAT distribution in diet-induced obese mice without side-effects. In short, this study provides clear evidence that TMC-based oral NPs can effectively improve celastrol for obesity treatment.
Keywords: Celastrol; Inflammation; N-trimethylated chitosan; Obesity; Oral targeting nanoparticles.
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