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

Abstract

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

“…To choose appropriate polymers for the SMSD system for TQM, the apparent solubility of TQM in water was studied in numerous concentrations of pre-dissolved polymers, including Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407. Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are frequently used as pharmaceutical excipients with amphiphilic properties to improve the solubility of poorly water-soluble medications due to their commercial availability and biocompatibility (Vasconcelos et al., 2017 ; Gangarde et al., 2020 ; Ilie et al., 2021 ). Due to interactions between lipophilic units of amphiphilic polymers and weakly water-soluble medicines, poorly soluble pharmaceuticals can become more soluble through encapsulation.…”

Impact of Methods of Preparation on Mechanical Properties, Dissolution Behavior, and Tableting Characteristics of Ibuprofen-Loaded Amorphous Solid Dispersions

“…Te aim was to select appropriate polymers for the IBP amorphous solid dispersion (ASD) system. Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 are frequently employed as carriers with amphiphilic characteristics to improve the solubility of poorly soluble drugs due to their biocompatibility and widespread availability in the commercial market [35][36][37]. As shown in Figure 1, the aqueous solubility of IBP increased as the polymer concentration increased.…”

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

“…The apparent solubility of TQM in water was tested in several concentrations of predissolved polymers such as Soluplus ® , Kolliphor ® P188, and Kolliphor ® P407 ranging from 5 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 [42][43][44]. Poorly water-soluble drugs can become more soluble through encapsulation owing to interactions between lipophilic units of amphiphilic polymers and poorly water-soluble drugs.…”