Tailoring Drug\nRelease Kinetics by the Design and\nOptimization of Substituents in Azobenzene Molecules in the Photosensitive\nLiposomal System

A light-sensitive\nmoiety, e.g., azobenzene, for the light-sensitive\nliposomal drug carrier has shown advantages as an advanced drug delivery\nsystem in site-specific smart therapy due to its reversible photoisomerization\ncharacteristics. In this work, a series of 4-position-cholesterol-functionalized\nazobenzene derivatives with 4′-position substituted pyridine,\nquinoline, isoquinoline, triethylamine, or ethylenediamine were synthesized,\nand the relationship between the molecular structure and drug release\nbehaviors was clarified. We found that the charge and electrophilicity\nof substituents were two important factors (expressed as the characteristic\ntime) that can precisely regulate the isomerization ratio in the liposomal\nsystem. There was an approximately linear correlation between the\ncharacteristic time of photoisomerization and the fitted first-order\nconstant of photoinduced drug release rate. The photoinduced drug\nrelease could be achieved at the desired time and in an appropriate\namount by tailoring the substituents at the 4′-position of\nazobenzene-cholesterol derivatives.