Characterization of pH-Responsive Self-Assembly Behaviors of Fatty Acid-Functionalized Prodrug

• Published in: Biochemical engineering journal 2020-12, Vol.164, p.107794, Article 107794
• Main Authors: Han, Jin, Hayashi, Keita, Okamoto, Yukihiro, Suga, Keishi, Umakoshi, Hiroshi
• Format: Article
• Language: English
• Subjects: Aggregation induced emission; Drug delivery system; Prodrug self-assembly
• ISSN: 1369-703X; 1873-295X
• DOI: 10.1016/j.bej.2020.107794

[Display omitted] •pH-responsive self-assembly behavior of Oxa-lipids was observed by designing fatty acid-like Oxaprozin prodrug.•Different self-assemble structures can be formed by Oxa-C6 and Oxa-C8 under various biological pH conditions.•Oxa-lipids showed enhanced fluorescence intensity after aggregated to fiber structure. Among possible drug delivery system (DDS) strategies, the prodrug-based self-assembly DDS (SADDS) has been paid much attention in terms of high loading and controlled release. In the application of SADDS, the properties and structures of self-assembly by prodrug molecules usually play important roles in their bioactivity. However, existing strategies to prepare various structures through prodrug molecular design seem to be insufficient. In this study, we investigated pH-responsive prodrug-based SADDSs as an alternate strategy, focusing on controlling self-assembly behavior via pH change and molecular structural design. The prodrug structure design was inspired by self-assembling fatty acids (FAs). Here, the aryl carboxylic acid Oxaprozin (Oxa), a primary non-steroidal anti-inflammatory agent, was selected as a model molecule to design Oxa-lipid prodrug molecules possessing carboxyl groups and different hydrocarbon chain lengths. This prodrug design strategy achieved control of the drug self-assembly behavior, changing from micelle to fiber to solid, which was responsive to pH conditions and molecular concentration. Thus, our proposed study may contribute to the development of a biological environment-sensitive SADDS.