Formation mechanism of herpetrione self-assembled nanoparticles based on pH-driven method

The self-assembled nanoparticles (SAN) formed during the decoction process of traditional Chinese medicine (TCM) exhibit non-uniform particle sizes and a tendency for aggregation. Our group found that the pH-driven method can improve the self-assembly phenomenon of Herpetospermum caudigerum Wall., and the SAN exhibited uniform particle size and demonstrated good stability. In this paper, we analyzed the interactions between the main active compound, herpetrione (Her), and its main carrier, Herpetospermum caudigerum Wall. polysaccharide (HCWP), along with their self-assembly mechanisms under different pH values. The binding constants of Her and HCWP increase with rising pH, leading to the formation of Her-HCWP SAN with a smaller particle size, higher zeta potential, and improved thermal stability. While the contributions of hydrogen bonding and electrostatic attraction to the formation of Her-HCWP SAN increase with rising pH, the hydrophobic force consistently plays a dominant role. This study enhances our scientific understanding of the self-assembly phenomenon of TCM improved by pH driven method.