Chitosan nanoparticles enhance the anti-inflammatory and anti-adipogenic effects of tart cherry anthocyanin in 3T3-L1 adipocytes

Obesity-associated adipose inflammation and gut dysfunction represent critical targets for dietary intervention. Tart cherry juice (TCJ)-derived anthocyanins (ACNs) exhibit potent anti-inflammatory and gut-protective bioactivity, but their poor stability and low oral bioavailability limit efficacy. Although nanotechnology can improve ACN delivery, conventional nanocarriers contain surfactants or emulsifiers that may impair gut health with chronic use. To overcome these challenges, we developed a surfactant-free nanoparticle platform using polysaccharides. Void nanoparticles (Vnano) were fabricated by ionic gelation of chitosan and carboxymethyl chitosan, followed by ACN adsorption through hydrogen bonding and electrostatic interactions to generate ACN-loaded nanoparticles (Tnano). Optimized Tnano achieved 80% ACN adsorption efficiency with spherical morphology (about 200 nm), narrow size distribution, and positive zeta potential (23 mV). Compared to free TCJ, Tnano demonstrated sustained ACN release, and fluorescence imaging showed dose- and temperature-dependent binding of the chitosan nanoparticles to 3T3-L1 preadipocytes. Tnano more effectively suppressed lipopolysaccharide (LPS)-induced inflammation, reducing interleukin-6 and monocyte chemoattractant protein-1 secretion by 39% (p < 0.0001) and 35% (p = 0.0316) in preadipocytes, and by 56.8% (p = 0.05) and 20% (p < 0.0001) in mature adipocytes, respectively, compared to LPS groups. Compared to control, Tnano reduced adipogenic lipid accumulation by 35%, versus only 14.2% for TCJ (p = 0.0003). As a proof of concept for future oral delivery applications, Tnano was encapsulated within an alginate hydrogel shell by electrospray to form a nano-in-micro format. This fully natural polysaccharide-based nanoplatform offers a strategy to enhance anthocyanin bioavailability and combat obesity-associated inflammation and metabolic disease.