Biological and Medicinal Chemistry

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


We report the synthesis of gemini-type amphiphilic molecules that form stable assemblies in aqueous medium. The assembly property of molecule M2 in aqueous solution 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, likely due to 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.


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