Co-Delivery of angiostatin and curcumin by a biodegradable polymersome for antiangiogenic therapy

Co-Encapsulated angiostatin (AS) and curcumin (Cur) in poly(ethylene glycol)-b-poly(epsilon-caprolactone) polymersomes (PEG-PCL-PMs) were prepared by film hydration method. The size and zeta potential of the prepared PEG-PCL-PMs were about 153 nm and -0.22 mV, respectively. Transmission electron microscopy was employed to confirm the polymersomal structure of PEG-PCL-PMs. In vitro drug release profiles showed a sustained release of angiostatin and curcumin from the dual-drug loaded polymersomes under physiological conditions (pH 7.4). In addition, confocal laser scanning microscopy and flow cytometry showed that drug-loaded polymersomes were delivered efficiently into the cytoplasm and nuclei of human microvascular endothelial cell line (HMEC-1) and then released active drugs in cells. Dual drug-loaded polymersomes (AS-Cur-PMs) remarkably inhibited proliferation and migration of HMEC-1 cells compared to those treated with the single drug. The chick chorioallantoic membrane assay showed that AS-Cur-PMs inhibited vessel sprouting in the chicken chorioallantoic membrane. Our data demonstrates a synergistic effect of angiostatin and curcumin in inhibiting angiogenesis, both in vitro and in vivo.