Polymeric micelles as drug delivery nanosystems: Moving towards improved stability

Polymeric micelles (PMs) have been identified as promising systems for nanodrug delivery due to their high solubilizing power, small size, long shelf life, good biocompatibility and high drug loading capacity. Despite their promising properties, PMs’ clinical translation remains hindered by two main challenges, instability under physiological conditions and regulatory requirements. Upon intravenous administration, PMs encounter a dynamic biological environment characterized by significant dilution, abrupt changes in pH, enzyme and ionic strength, contact with various macromolecules (proteins, lipids), and shear forces that affect their surface properties. These changes can disrupt the balance of the PM system, compromising the integrity of the micelles. Several attempts have been made to avoid these changes, including cross-linking approaches, stimuli-responsive PMs and polymer-drug conjugates. This review provides an insight into the most promising techniques to improve micelle stability and drug retention, enhancing the therapeutic efficacy of drugs and paving the way for PMs’ clinical translation.