Physical hydrogels with self-assembled nanostructures as drug delivery systems

Introduction: As an essential complement to chemically crosslinked hydrogels, drug delivery systems based on physical hydrogels with self-assembled nanostructures are gaining increasing attention, owing to potential advantages of reduced toxicity, convenience of in situ gel formation, stimuli-responsiveness, reversible sol-gel transition, and improved drug loading and delivery profiles. Areas covered: In this review, drug delivery systems based on physical hydrogels are discussed according to their self-assembled nanostructures, such as micelles, layer-by-layer constructs, supramolecular inclusion complexes, polyelectrolyte complexes and crystalline structures. The driving forces of the self-assembly include hydrophobic interaction, hydrogen bonding, electrostatic interaction, pi-pi stacking and weak van der Waals forces. Stimuli-responsive properties of physical hydrogels, including thermo-and pH-sensitivity, are considered with particular focus on self-assembled nanostructures. Expert opinion: Fabricating self-assembled nanostructures in drug delivery hydrogels, via physical interactions between polymer-polymer and polymer-drug, requires accurately controlled macro-or small molecular architecture and a comprehensive knowledge of the physicochemical properties of the therapeutics. A variety of nanostructures within hydrogels, with which pay-loads may interact, provide useful means to stabilize the drug form and control its release kinetics.