Amphiphilic Small-Molecule Assemblies to Enhance the Solubility and Stability of Hydrophobic Drugs.

Amphiphilic assemblies made from diverse synthetic building blocks are well known for their biomedical applications. Here, we report the synthesis of gemini-type amphiphilic molecules that form stable assemblies in water. The assembly property of molecule M2 in aqueous solutions was first inferred from peak broadening observed in the proton NMR spectrum. This was supported by dynamic light scattering and transmission electron microscopy analysis. The assembly formed from M2 (M2agg) was used to solubilize the hydrophobic drugs curcumin and doxorubicin at physiological pH. M2agg was able to effectively solubilize curcumin as well as protect it from degradation under UV irradiation. Upon solubilization in M2agg, curcumin showed excellent cell permeability and higher toxicity to cancer cells over normal cells, probably because of enhanced cellular uptake and increased stability. M2agg also showed pH-dependent release of doxorubicin, resulting in controlled toxicity on cancer cell lines, making it a promising candidate for the selective delivery of drugs to cancer cells.