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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\u2014acetaminophen (ACP), fluconazole (FCZ), and proglumide (PGM), respectively\u2014were 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\u2013base properties critically modulate SP morphology and release behavior, highlighting the importance of drug\u2013biomaterial interactions in designing SP-based delivery platforms.<\/jats:p>","DOI":"10.1021\/acsabm.6c01613","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:02:08Z","timestamp":1791187328000},"page":"9916-9931","source":"Crossref","is-referenced-by-count":0,"title":["Drug-Dependent Disruption of Amyloid Nanofibril-Mediated Wrinkling in Supraparticle Assemblies"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8269-1465","authenticated-orcid":true,"given":"Yuzuki","family":"Nakayama","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University , , 4-20-1 Nasahara , , ,","place":["Takatsuki, Osaka, Japan, 569-1094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Shimozono","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University , , 4-20-1 Nasahara , , ,","place":["Takatsuki, Osaka, Japan, 569-1094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8333-4900","authenticated-orcid":true,"given":"Tero","family":"K\u00e4m\u00e4r\u00e4inen","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , , Egerlandstra\u00dfe 1 , ,","place":["Erlangen, Germany, 91058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Koike","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University , , 4-20-1 Nasahara , , ,","place":["Takatsuki, Osaka, Japan, 569-1094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-7425","authenticated-orcid":true,"given":"Ryoma","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University , , 4-20-1 Nasahara , , ,","place":["Takatsuki, Osaka, Japan, 569-1094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University , , 4-20-1 Nasahara , , ,","place":["Takatsuki, Osaka, Japan, 569-1094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4091-4451","authenticated-orcid":true,"given":"Yuichi","family":"Tozuka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Osaka Medical and Pharmaceutical University , , 4-20-1 Nasahara , , ,","place":["Takatsuki, Osaka, Japan, 569-1094"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3370-6662","authenticated-orcid":true,"given":"Kazunori","family":"Kadota","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Wakayama Medical University , , 25-1 Shichiban-cho , , ,","place":["Wakayama-shi, Wakayama, Japan, 640-8156"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"2026101904080849900_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apt.2026.105265","article-title":"Recent Advances of Macroporous Architectures for Multidisciplinary Applications","volume":"37","author":"Abdillah","year":"2026","journal-title":"Adv. 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