Role of substitution degree in thiol-modified hyaluronic acid in enhancing the physical stability of curcumin-loaded zein nanoparticles

Thiol-modified hyaluronic acid (HASH) improves zein nanoparticles (ZNPs) stability by disulfide bonding with zein. However, the effect of the degree of thiol substitution in HASH on the stability of the ZNPs remains unclear. In this study, HASH with 1%, 3%, and 5% degrees of thiol substitution was synthesized and used as stabilizers to prepare three composite NPs. The pH and salt ion stability of the composite NPs increased with increasing degree of thiol substitution, which improved the antioxidant and anti-inflammatory capacities of the composite NPs. Interestingly, when the degree of thiol substitution exceeded 3%, the physical stability of composite NPs did not improve further. Our results revealed the relationship between the degree of thiol substitution in HASH and the stability of ZNPs, and provided the optimal degree of thiol substitution. These findings provided important information for improving the physical stability of ZNPs and contributed to the development of a delivery system for natural actives.