Biodegradable micelles self-assembled from miktoarm star block copolymers for MTX delivery

Biodegradable micelles based on disulfide-linked monomethoxy poly(ethylene glycol)-b-poly(methyl methacrylate)(2) (mPEG-SS-PMMA(2)) miktoarm star block copolymers were synthesized through atom transfer radical polymerization procedure and applied to solubilization and delivery of methotrexate (MTX). The synthesized miktoarm star block copolymers were characterized by H-1 nuclear magnetic resonance, Fourier transform infrared spectra, and gel permeation chromatography. The block copolymers were able to self-assemble into spherical micelles in water with an average diameter up to 130 nm by transmission electron microscopy observation and dynamic light scattering measurements and have a critical micelle concentration of 0.91 mg/L. When MTX was incorporated into obtained micelles, high drug loading capacity was found attributed to the designed miktoarm star-shaped nanostructure. Interestingly, in presence of dithiothreitol, the micelles could be degraded into polymer chains by cleavage of the disulfide linkages. The in vitro release studies revealed that these micelles released over 95 % of MTX within 48 h under a reductive environment analogous to that of the cell comparing to minimal drug release (< 22 %) under nonreductive conditions. Cell cytoxicity experiments showed that the obtained micelles exhibited nontoxic, and the drug-loaded micelles exhibited high anticancer efficacy and better biocompatibility as compared to free MTX. All of these results showed that mPEG-SS-PMMA(2) micelles are promising carriers for delivery of hydrophobic antitumor drugs.