Cross-linked polymeric micelles based on block ionomer complexes

Polymeric micelles formed as a result of the self-assembly of block copolymers constitute an important class of supramolecular structures that attracted attention as drug carriers in drug delivery and nanomedicine. Chemical stabilization of the polymeric micelles by introducing cross-links between block copolymer chains can increase stability and prevent premature disintegration of these micelles in the body. The cross-linking strategy has been also applied to a special class of polymeric micelles formed by block copolymers with ionic and nonionic water-soluble segments (block ionomers) that are electrostatically coupled with oppositely charged species. Such polyion complex micelles (also termed block ionomer complexes) have high colloidal stability due to steric repulsion of their corona and often assume a spherical core-shell morphology. These species are currently actively researched for the delivery of various low molecular weight drugs and protein or nucleic acid-based therapeutics. This paper highlights recent advances in the development of cross-linked polymeric micelles, the physicochemical aspects of the formation and behavior of various block ionomer complexes, the strategies for the cross-linking of core and shell parts of the micelles, and the advantages and major challenges in their biomedical applications.