Hydrophobicity of acyl groups in alpha-cyclodextrin-threaded polyrotaxanes dominates the formation and stability of self-assembled nanoparticles

摘要

Five series of acylated polyrotaxanes (PRXs) with different acyl groups (acetyl, propionyl, butyryl, valeryl, and benzoyl) were synthesized to investigate their solubility in aqueous solutions and the formation and stability of self-assembled nanoparticles. Acetylated PRXs (Ac-PRXs), propionylated PRXs (Pr-PRXs), and butyrylated PRXs (Bu-PRXs) dissolved in water, and yielded transparent solutions at a low degree of substitution, whereas nanoparticle formation was observed when the degree of substitution exceeded the threshold values (34% for Ac-PRXs, 18% for Pr-PRXs and 11% for Bu-PRXs). Pr-PRX and Bu-PRX nanoparticles exhibited low critical micelle concentration compared to Ac-PRXs. Valeryl or benzoyl group-modified PRXs precipitated in aqueous solutions due to their strong hydrophobicity. The loading efficiency of hydrophobic drugs in Pr-PRX nanoparticles improved significantly compared to those in Ac-PRX nanoparticles. Collectively, the moderate hydrophobicity of the acyl groups is optimal for the formation of stable self-assembled nanoparticles in aqueous solutions and efficient encapsulation of hydrophobic drugs.