Chitosan–Alginate Nanoparticle System for the Delivery of Cocoa Polyphenols for Diabetes and Obesity Management

Phenolic-rich extracts from Theobroma cacao are obtained under different solvent extraction conditions, that is, with ethanol solo (first-stage extract [FSE]) and with ethanol-acetone in two steps (second-stage extract [SSE]) to maximize bioactive compound recovery. Among the evaluated solvents, acetone yields the highest total phenolic content (532.57 ?g GAE/g), and the corresponding extract exhibited strong inhibitory activity against ?-glucosidase (IC 50 = 4.04 ?g/mL) and lipase (IC 50 = 14.034 ?g/mL), highlighting its potential role in the prevention of metabolic diseases. However, phenolic compounds often present limited stability and bioavailability, which may restrict their practical application. To address this limitation, cocoa phenolic extracts were encapsulated within chitosan–alginate nanoparticles (CANPs) using a polyelectrolyte complexation approach. The obtained nanoparticles exhibited particle sizes ranging from 328.5 to 454.9 nm for FSE and SSE formulations, respectively, along with high absolute zeta potential values (> |32| mV), indicating good colloidal stability. The extraction method significantly influenced the encapsulation efficiency (EE), with SSE-CANPs showing substantially higher EE (64.45% ± 0.49%) compared to FSE-CANPs (33.93% ± 0.24%). The in vitro release of phenolic compounds was evaluated under simulated gastrointestinal conditions. The total cumulative release remained below 50%, indicating high resistance to rapid degradation and enabling a sustained release profile under varying pH conditions.