Fabrication of Mixed Polymeric Micelles Based on Stimuli-Responsive Amphiphilic Copolymers for Drug Delivery and Controlled Release

Abstract

In this report, mixed polymeric micelles (MPMs) system self-assembled from two kinds of cholesterol-grafted amphiphilic block copolymers cholesterol modified poly ([Formula: see text]-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-[Formula: see text]-Chol) and poly([Formula: see text]-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-[Formula: see text]-mPEG-Chol) were prepared for drug delivery and controlled release with pH and redox-responsibilities. The self-assembly of two block copolymers was evaluated by measurement of critical micelle concentration (CMC) values using fluorescence spectroscopy. The hydrodynamic diameter, polydispersity index (PDI) and zeta-potential of MPMs in aqueous were recorded by dynamic light scattering (DLS) at different conditions. Doxorubicin (DOX) was efficiently encapsulated in the micellar core by the hydrophobic interaction. The drug loading content (LC) and encapsulation efficacy (EE) of MPMs with different formulations were evaluated. The DOX was released due to the swelling and disassembly of MPMs induced by low pH and high glutathione (GSH) concentrations. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values and reducing agents. The results showed that the MPMs could be the potential anticancer drug delivery carriers with pH/redox-triggered drug release profile.