Facile fabrication of double-walled polymeric hollow spheres with independent temperature and pH dual-responsiveness for synergetic drug delivery

A dual-responsive double-walled polymeric hollow sphere (PHS) serving as a candidate for synergetic drug delivery platform is prepared by a simple and green template polymerization in aqueous medium. The PHS, comprised of thermo-responsive crosslinked poly( N -isopropylacrylamide) (PNIPAM) as the inner shell and pH-responsive crosslinked poly(methacrylic acid) (PMAAc) as the outer shell, is assembled through self-removal of the thermo-responsive template from a core-triple shell structure by free radical polymerization with sequential addition of reactants. The discrete double-shell structure renders the PHS independent temperature and pH-controlled swelling/shrinking capability. Taking the advantage of two compartmentalized internal spaces (the core and the interlayer spaces) with independent temperature- and pH-dependent behaviors, two model drugs representing the small molecule and the macromolecule are loaded in selective locations of the PHS. Two drugs show dramatically different release profiles according to environmental temperature and pH, due to the localization of drugs and the stimuli-dependent property of its protective shells. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 44335.