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.