Tuning the molecular weight of polymeric amphiphiles as a tool to access micelles with a wide range of enzymatic degradation rates

In the last two decades nano-sized assemblies such as polymeric micelles have emerged as promising candidates for the use as smart drug delivery systems and other bio-medical applications. In order to use such assemblies in the field of drug delivery, it is not sufficient for micelles to be able to encapsulate or covalently bind drug molecules, and they must have a release mechanism as well. Due to this reason, there is very rich variety of reports that are focused on stimuli responsive polymeric micelles. Commonly, light, pH or temperature changes, trigger a change in the polymer characteristics that cause in turn the disassembly of the micelles. More recently enzymes were utilized as triggers for the disassembly of polymeric micelles. Enzymes can be highly beneficial as triggers for the disassembly of drug containing polymeric micelles due to their specificity, catalytic nature and the fact that in some cases specific enzymes are overexpressed and secreted into the extracellular matrix in diseased tissues. In spite of the great potential, there are still many challenges that keep such smart systems from reaching clinical uses, and hence it is important to study their behavior and characteristics. Regularly, polymeric micelles are formed from the self-assembly of amphiphilic di-block copolymers in aqueous media. The general and trivial assumption is that micellar stability rises as the hydrophobic block weight percentage increases. In this work, we demonstrate that the total molecular weight of polymeric amphiphiles, with similar hydrophilic/ hydrophobic ratio, can have tremendous effect in terms of enzymatic activation rate, micellar diameter and encapsulation capacity of hydrophobic cargo.