Amphiphilic copolymers modified with oleic acid and cholesterol by combining ring opening polymerization and click chemistry with improved amphotericin B loading capacity

Polymer micelles obtained from amphiphilic copolymers have emerged as promising drug vehicles given their nanometric size, simple release, and encapsulation mechanisms. Nevertheless, their lack of functional groups that interact with the drugs causes low encapsulation capacities. In this paper, the synthesis of an amphiphilic copolymer composed of polyethylene glycol and a poly(ester-co-carbonate) segment containing alkyne groups, as well as its coupling in a post-synthesis stage with other azido-functionalized substances through click reaction, is reported. The modifiers can be intentionally selected to favor polymer–drug compatibility for the rational development of drug delivery systems. Herein, amphotericin B was taken as a model because it is a water-insoluble and highly toxic drug. Cholesterol and oleic acid were employed as modifiers of the copolymers and provided improvements on the drug loading capacity compared with an unmodified copolymer. While oleic acid modified structures presented the highest encapsulation when five units were grafted; a single cholesterol molecule gave the highest enhancement.