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

Abstract

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 (M2<sub>agg</sub>) was used to solubilize the hydrophobic drugs curcumin and doxorubicin at physiological pH. M2<sub>agg</sub> was able to effectively solubilize curcumin as well as protect it from degradation under UV irradiation. Upon solubilization in M2<sub>agg</sub>, curcumin showed excellent cell permeability, and higher toxicity to cancer cells over normal cells, likely due to enhanced cellular uptake and increased stability. M2<sub>agg</sub> 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.

Self-Micellizing Solid Dispersion of Thymoquinone with Enhanced Biopharmaceutical and Nephroprotective Effects

“…The apparent solubility of TQM in water was tested in the presence of several concentrations of pre-dissolved polymers such as Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 ranging from 2 to 25 mg/mL in the present study for the selection of suitable polymers in the SMSD system for TQM. Because of their commercial availability and biocompatibility; Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are commonly utilized as pharmaceutical excipients with amphiphilic characteristics to increase the solubility of poorly water-soluble medicines (Gangarde et al, 2020;Ilie et al, 2021;Vasconcelos et al, 2017). Poorly water-soluble drugs can become more soluble through encapsulation owing to interactions between lipophilic units of amphiphilic polymers and poorly water-soluble drugs.…”