Enhancing drug delivery in migraine therapy: A study on natural small molecule co-assembly

Migraine is one of the most common and debilitating neurological disorders worldwide, and neurogenic inflammation is thought to be a key factor. More recently, natural carrier-free co-assemblies of small molecules have been shown to be an effective new type of therapeutic system. This study developed nanoparticles co-assembled with oleanolic acid (OA) and evodiamine (Evo), based on active ingredients from traditional Chinese medicine, with a particle size of approximately 380 nm and a surface charge of approximately −14.6 mV. The analysis of the assembly mechanism shows that the co-assembly of OA and Evo (OA-Evo CNPs) is mainly mediated by hydrogen bonding interactions, π-π stacking and hydrophobic interactions. The physicochemical characterisation demonstrated that the OA-Evo CNPs exhibited favourable hydrophilic properties, slow-release characteristics, and in vitro safety. The co-assembly of nanoparticles has been demonstrated to exert a substantial improvements effect on nitroglycerin-induced migraine-like behaviour in mouse models, as evidenced by the observation of significant improvements in biochemical (NO, 5-HT, and CGRP, etc) and inflammatory markers (TNF-α、IL-1β and IL-6) in the plasma, along with a notable reduction in microglia activation within the brain tissue of test subjects. This study proposes a strategy for co-assembly of natural small molecules and highlights the synergistic effect of the combined plant compounds.