Self-assembly of pH-sensitive mixed micelles based on linear and star copolymers for drug delivery

The mixed micelles constructed from the star and linear copolymers were transformed from a core–shell structure into a core–shell–corona one with pH value. [Display omitted] ► pH-sensitive mixed micelles were readily formed by comicellization of two copolymers. ► The mixed micelles could be kept stable in wide pH range. ► The mixed micelles exhibited low cytotoxicity and high positive zeta potential. ► An increase in pH accelerated the release of drug from mixed micelles in vitro. Comicellization of a star block copolymer poly( ε-caprolactone)- block-poly(diethylamino)ethyl methacrylate (S(PCL- b-PDEAEMA)) and a linear block copolymer methoxy poly(ethylene glycol)- block-poly( ε-caprolactone) (mPEG- b-PCL) was developed to enhance the stability and lower the cytotoxicity of the micelles. The two copolymers self-assembled into the mixed micelles with a common PCL core surrounded by a mixed PDEAEMA/mPEG shell in aqueous solution. This core–shell structure was transformed to the core–shell–corona structure at high pH due to the collapse of the PDEAEMA segment. The properties of the polymeric micelles were greatly dependent on the weight ratio of the two copolymers and the external pH. As increasing the mPEG- b-PCL content, the size and the zeta potential of the mixed micelles were lowered while the pH-dependent stability and the biocompatibility were improved. Moreover, an increase in pH accelerated the release of indomethacin (IND) from the mixed micelles in vitro. These results augured that the mixed micelles could be applied as a stable pH-sensitive release system.