Nano-encapsulation of Folic Acid into Chitosan–Sodium tripolyphosphate Nanoparticles: Synthesis, Characterization, and Controlled Release Kinetics

Background and Objective: Folic acid, an essential B-group vitamin, plays a pivotal role in DNA synthesis, cell division, and tissue development. However, its high sensitivity to environmental factors such as light, temperature, pH, and oxidation significantly limits its stability and practical use in food and pharmaceutical formulations. To overcome these limitations and enhance its bioavailability, the development of controlled-release delivery systems based on biodegradable polymers such as chitosan has attracted considerable interest. This study aimed to fabricate chitosan–sodium tripolyphosphate (TPP) nanoparticles encapsulating folic acid via the ionic gelation technique and to evaluate their physicochemical, structural, and release characteristics. Materials and Methods: Chitosan nanoparticles were prepared through ionic gelation using sodium TPP as a cross-linking agent, with folic acid encapsulated during nanoparticle formation. The morphology and size of the synthesized nanoparticles were characterized using field emission scanning electron microscopy (FESEM), while surface charge was determined by zeta potential analysis. And to confirm the chemical interactions and the formation of intermolecular bonds among chitosan, folic acid and sodium tripolyphosphate, Fourier transform infrared spectroscopy (FTIR) was employed to investigate potential interactions between chitosan and folic acid. Encapsulation efficiency was quantified spectrophotometrically. The in vitro release behavior of folic acid was monitored under ambient conditions over a 30-day period, and the release kinetics were analyzed using various mathematical models, including Higuchi, Peppas, first-order, and zero-order equations. Results: FESEM images revealed uniform, spherical nanoparticles in both blank and folic acid-loaded formulations. The average particle size increased from 39 nm for blank nanoparticles to 360 nm after folic acid incorporation, likely due to increased suspension viscosity. Zeta potential measurements indicated a positive surface charge sufficient to maintain colloidal stability, despite a slight reduction following folic acid loading. FTIR spectra exhibited characteristic peak shifts and intensity changes, confirming the successful encapsulation of folic acid within the chitosan matrix without altering the polymer backbone. The encapsulation efficiency reached 91%, demonstrating excellent formulation performance. The release profile showed a slow and sustained release pattern, with approximately 28% of the folic acid released after 30 days. Kinetic modeling revealed that the Peppas equation provided the best fit (R² = 0.97), indicating that Fickian diffusion was the predominant release mechanism. Conclusion: Overall, chitosan–TPP nanoparticles exhibited favorable physicochemical properties, high encapsulation efficiency, and a prolonged, controlled-release profile of folic acid. These findings suggest that the developed nanoparticles represent a promising and stable carrier system for targeted and sustained delivery of folic acid in food, nutraceutical, and pharmaceutical applications.