Drug loading and release kinetics in polymeric micelles: Comparing dynamic versus unimolecular sugar-based micelles for controlled release

Amphiphilic macromolecules, possessing sugar-based hydrophobic and poly(ethylene glycol) hydrophilic domains, provide tunable structures that form effective polymeric micellar drug delivery systems. In this work, we compare traditional dynamic micelles and covalently bound unimolecular amphiphilic macromolecule micelles to study the effects of amphiphilic macromolecule hydrophobic domain branching, micelle architecture, and hydrodynamic volume of two drugs (triclosan and suloctidil) to elucidate the micellar structure–property relationships that govern drug loading and release kinetics. Overall, more hydrophobic micelles with either longer amphiphilic macromolecule alkyl side chains or a higher degree of hydrophobic domain branching exhibited increased triclosan loading compared to less hydrophobic micelles with smaller amphiphilic macromolecule hydrophobic domains. However, varying levels of micelle hydrophobicity did not significantly change suloctidil loading, where only minimal loading differences were seen between micelles with highly hydrophobic and less hydrophobic domains. In both dynamic and unimolecular micelles, the loading extent was primarily drug volume-dependent, where the smaller triclosan molecules demonstrated increased loading and sustained release compared to the larger suloctidil molecules. Unimolecular micelles followed a similar trend with generally higher loading capacities compared to dynamic micelles. Release characteristics for both amphiphilic macromolecule micelle types demonstrated little correlation to the amphiphilic macromolecule chemistry or micelle architecture and were instead primarily drug-dependent, with suloctidil- and triclosan-loaded micelles following the Korsmeyer–Peppas and Weibull models, respectively. The micelle structure–property relationships identified herein allow for improved drug–micelle compatibility to optimize drug delivery systems for poorly water-soluble drugs.