Amphiphilic depsipeptide-based block copolymers as nanocarriers for controlled release of ibuprofen with doxorubicin

Well-defined amphiphilic multiblock copolymers PDMAEMA-b-P(IBMD-co-PDO)-b-PEG-b-P(IBMD-co-PDO)-b-PDMAEMA [PDMAEMA-PIBMD-PPDO-PEG], based on poly(2-(dimethylamino)ethyl methacrylate) block (PDMAEMA), poly(3(S)-isobutyl-morpholine-2,5-dione-co-p-dioxanone) block (P(IBMD-co-PDO)), and poly(ethylene glycol) block (PEG) were successfully synthesized by combination of ring-opening polymerization (using 3(S)-isobutyl-morpholine-2,5-dione and p-dioxanone initiated by hydroxyl end of PEG) and atom transfer radical polymerization (ATRP). Furthermore, all these copolymers were characterized by 1H NMR, 13C NMR, Fourier transformed-infrared, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis measurements. The degradation experiments showed that the molecular weight of PDMAEMA-PIBMD-PPDO-PEG decreased along with degradation time. In addition, these copolymers could readily self-assemble into nanosized microspheres in phosphate buffered solution. Ibuprofen (IBU) and doxorubicin (DOX) as a kind of combined model drugs were loaded into these microspheres by the combination of ionic interaction and hydrophobic effect. These copolymer microspheres exhibited high loading capacity (LC, up to 26.88%), encapsulation efficiency (EE, up to 61.29%), and sustained release behavior of IBU-DOX in phosphate buffered solution. The results of transmission electron microscopy and dynamic light scattering showed that the microspheres were well-defined uniform spherical particles with average diameter less than 120 nm. Therefore, it can be envisaged that these copolymer systems are promising candidates for controlled release application. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3213-3226