Driving co-precipitation of hydrophobic drugs in water by conjugating alkyl chains

Co-precipitated nanoaggregates (NAs) of small-molecule hydrophobic drugs have been widely used as carrierfree drug co-delivery systems, but how to construct stable NAs for potential co-delivery of combination drugs has been remaining unclear. Herein, we performed such investigation using our previously reported fluorescence resonance energy transfer (FRET) method, which was based on the fluorescent hydrophobic drugs of camptothecin (CPT), curcumin (CUR), and their lipophilic derivatives containing different alkyl chains. It is shown that unmodified CPT and CUR failed to form stable co-assembling NAs. Increasing hydrophobicity of one drug by conjugating an alkyl chain could promote the co-assembling ability of CPT and CUR, but the resulting NAs were very unstable and undergone a burst disassembly in the plasma. Only simultaneously enhancing the hydrophobicity of CPT and CUR could obtain stable co-assembling NAs. These results highlighted the co-assembly and disassembly of NAs formed by various hydrophobic drugs, which can effectively guide the design of coassembling small-molecule drug co-delivery systems with high stability to resist the dilution of blood after intravenous injection.

Automated summary

The study investigated the stability of co-assembling nanoaggregates using a fluorescence resonance energy transfer method, finding that only by simultaneously increasing the hydrophobicity of both camptothecin and curcumin could stable co-assembling NAs be obtained. This highlights the importance of co-assembly and disassembly of NAs formed by various hydrophobic drugs for designing stable co-delivery systems resistant to blood dilution after intravenous injection.