Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery

The formation of polymeric micelles in aqueous environments through the self-assembly of amphiphilic polymers can provide a versatile platform to increase the solubility and permeability of hydrophobic drugs and pave the way for their administration. In comparison to various self-assembly-based vehicles, polymeric micelles commonly have a smaller size, spherical morphology, and simpler scale up process. The use of polymer-based micelles for the encapsulation and carrying of therapeutics to the site of action triggered a line of research on the synthesis of various amphiphilic polymers in the past few decades. The extended knowledge on polymers includes biocompatible smart amphiphilic copolymers for the formation of micelles, therapeutics loading and response to external stimuli, micelles with a tunable drug release pattern, etc. Different strategies such as ring-opening polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain-transfer, nitroxide mediated polymerization, and a combination of these methods were employed to synthesize copolymers with diverse compositions and topologies with the proficiency of self-assembly into well-defined micellar structures. The current review provides a summary of the important polymerization techniques and recent achievements in the field of drug delivery using micellar systems. This review proposes new visions for the design and synthesis of innovative potent amphiphilic polymers in order to benefit from their application in drug delivery fields.