Enhanced Colon-Targeted Release of Propolis by pH-driven Encapsulation using Folic Acid Modified Carboxymethyl Chitosan

Propolis is a natural bioactive compound that is being explored as a nutraceutical because of its potential health benefits. In this study, propolis-loaded biopolymer nanoparticles were fabricated from folic acid-modified carboxymethyl chitosan (FA-CMCS) using the pH-driven method. The mean diameter of the propolis-loaded FA-CMCS nanoparticles was about 180 nm, and transmission electron microscopy showed they had a spherical shape. Fourier transform infrared spectroscopy analysis demonstrated that hydrogen bonding, electrostatic, and hydrophobic interactions were the major driving forces responsible for nanoparticle formation. The nanoparticles had good colloidal stability at pH 2.0, 3.0, 7.0, and 8.0 but exhibited some aggregation at intermediate pH values. The nanoparticles were also stable to salt addition up to 400 mM NaCl. Propolis-loaded FA-CMCS nanoparticles exhibited improved antioxidant properties compared to pure propolis and propolis-free nanoparticles. A simulated digestion model (fed state conditions) indicated that different amounts of propolis were released in different gastrointestinal regions: around 25%, 15%, and 25% in the stomach, small intestine, and colon, respectively. Our results suggest that the nanoparticles fabricated in this study have potential as colloidal delivery systems for sustained release of propolis in the human gut.