Yuzuki Nakayama

Supraparticles (SPs) are secondary particles formed through nanoparticle self-assembly with porous architectures and bioinspired structural features suitable for drug delivery applications. Although binder-mediated structural control influences SP assembly, how different loaded drugs systematically alter amyloid nanofibril (ANF) and SP structures remains unclear. In this study, neutral, basic, and acidic model drugs—acetaminophen (ACP), fluconazole (FCZ), and proglumide (PGM), respectively—were incorporated into spray-dried SPs composed of silica nanoparticles (SiNPs) and ANFs to investigate the effects of drug properties on SP structure and release behavior. All drugs exhibited nearly 100% loading efficiency, and powder X-ray diffraction analysis revealed that they were in an amorphous state within the SPs. ACP- and FCZ-loaded SPs maintained their characteristic ANF-induced wrinkled morphology, whereas PGM-loaded SPs exhibited a pronounced loss of wrinkling at pH 2, indicating that acidic drugs can disrupt ANF-mediated assembly during SP formulation. Drug release studies further showed that ANFs suppressed the initial burst release and slowed the overall release by restricting diffusion pathways within the SP structures. This suppression was the most pronounced in PGM-loaded SPs, likely owing to drug retention within the assembled ANF domains. These findings demonstrate that drug acid–base properties critically modulate SP morphology and release behavior, highlighting the importance of drug–biomaterial interactions in designing SP-based delivery platforms.