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To address these challenges, we developed a novel hybrid drug delivery platform\u2014lipidic prodrug co\u2010crystals (LPCCs)\u2014that combines the benefits of lipidic self\u2010assembly and pharmaceutical co\u2010crystallization. In this study, a lipidic prodrug is synthesized by linking catechol\u2010containing \u03b1\u2010aminophosphonate with phenylboronic acid\u2010modified bifonazole (Bfz), an antifungal agent, via boronate bonding. The resulting self\u2010assembled structures exhibit high drug\u2010loading capacity (up to 85%) and are capable of co\u2010crystallizing with anti\u2010inflammatory agents such as nonsteroidal antiinflammatory drugs (NSAIDs) through strong aromatic and ionic interactions. This dual\u2010delivery system enables the controlled, site\u2010specific release of both antifungal and anti\u2010inflammatory agents in response to the acidic and oxidative microenvironment of fungal biofilms. LPCCs effectively prevent biofilm formation, eradicate mature biofilms, and enhance ROS\u2010scavenging capacity. Mechanistically, LPCCs inhibit the NF\u2010\u03baB\/COX\u20102 pathway, reduce pro\u2010inflammatory cytokines, and promote an anti\u2010inflammatory M\n                    <jats:sub>2<\/jats:sub>\n                    macrophage phenotype. In a murine rectal candidiasis model, LPCCs significantly reduced fungal load, restored tissue integrity, and normalized immune and microbial environments. Our findings highlight LPCCs as a promising strategy for enhancing treatment efficacy, improving patient compliance, and overcoming the limitations of current antifungal therapies.\n                  <\/jats:p>","DOI":"10.1002\/adma.202510382","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T12:13:39Z","timestamp":1754655219000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lipidic Prodrug Co\u2010Crystals: A Platform for Combination Therapy Targeting Fungal Biofilms"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1738-7857","authenticated-orcid":false,"given":"Yong","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology Nankai University  Tianjin 300071 China"},{"name":"Translational Medicine Laboratory the First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang 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