Polymeric Micelles for Nanomedicine: How to Enhance Their Stability?

Polymeric micelles remain actively studied objects in the nanomedicine, including the anticancer pharmacotherapy, for several decades. Due to their "core-corona" structure, adjustable parameters (i.e. size, shape, sorption capacity, degradation rate, etc.), the ability to impart stimuli-sensitive properties, etc., polymeric micelles have proven themselves as promising carriers that are capable of effective encapsulation of various drug substances, their delivery to target tissues and organs, while ensuring their controlled and prolonged release. Despite numerous studies, only four nanopreparations of anticancer agents based on polymeric micelles have been approved in different parts of the world to date. The presented review discusses one of the significant disadvantages of polymeric micelles as drug carriers, namely the chance of their disintegration into unassociated macromolecules upon dilution and/or environmental conditions changes (pH, temperature, ionic strength of the solution), and considers some strategies used to eliminate this disadvantage due to insufficient thermodynamic stability. The strategies include chemical cross-linking of polymeric chains that form the core or corona of micelles, physical cross-linking of micelle segments due to additional hydrophobic, electrostatic interactions or stereocomplexation, and the formation of monomolecular micelles.