Polymeric Micelles for Nanomedicine: How to Enhance Their Stability?

For several decades, polymeric micelles remain to be objects actively studied in the field of nanomedicine, including the anticancer pharmacotherapy. Due to their “core–corona” structure, adjustable parameters (i.e., size, shape, sorption capacity, degradation rate, etc.), the possibility to impart stimuli-sensitive properties, etc., polymeric micelles have proven themselves to be promising carriers that can efficiently encapsulate various drugs and deliver them to targeted tissues and organs, providing controlled and prolonged release of the drugs. Despite the numerous studies, only four nanoforms of anticancer agents based on polymeric micelles have been approved in different regions of the world to date. This review discusses one of the significant disadvantages of polymeric micelles as drug carriers, namely the possibility of their disintegration into unassociated macromolecules upon an abrupt dilution and/or a change in ambient conditions (pH, temperature, solution ionic strength, etc.) due to their insufficient thermodynamic stability. Some strategies used to eliminate this disadvantage are considered. They include chemical cross-linking of polymeric chains that form the cores or coronas of micelles, physical crossl-inking of micelle segments via additional hydrophobic and electrostatic interactions or stereocomplexation, and the formation of so-called monomolecular micelles.