Promotion of Micelle Stability via a Cyclic Hydrophilic Moiety
Abstract
Polymeric micelles represent one of the most investigated drug delivery systems due to the capability to increase the solubility and circulation time of lipophilic drugs. However, the stability of micelles in the blood circulation remains the substantial challenge for their clinical translations because the drug-loaded micelles must show sufficient stability to survive the extremely dilution in the blood after injection, which is crucial for minimizing the off-target-associated side effect and for promoting in vivo long circulation. For this purpose, herein we reported a novel strategy to improve the micelle stability by altering the topological structure of polymer species. Specifically, the cyclic (c) topology was introduced into the hydrophilic moiety of the amphiphilic block copolymers composed of hydrophilic poly(oligo eth-ylene glycol) methacrylates (POEGMA) and hydrophobic poly(ε-caprolactone) (PCL), resulting in a tadpole-like block copolymer of (c-POEGMA)-b-PCL. Interestingly, the micelles self-assembled from (c-POEGMA)-b-PCL copolymers showed lower critical micelle concentration (CMC), smaller size, slower in vitro drug release profile and less in vitro cytotoxicity against HeLa cells than the micelles formed by the linear (l) counterparts of (l-POEGMA)-b-PCL, which demonstrates the greater stability of (c-POEGMA)-b-PCL micelles relative to (l-POEGMA)-b-PCL analogues. This work thus reveals that the cyclic hydrophilic moiety can offer extra stability for the self-assembled micelles, which provides an alternative to fabricate polymeric micelles toward enhanced stability for in vivo applications.
