Dual-modified bufalin loaded liposomes for enhanced tumor targeting

Abstract Bufalin, a traditional oriental medicine, has been incorporated into liposomes for better targeted drug delivery. Bufalin-loaded liposome (L-BF), bufalin-loaded PEGylated liposome (L-PEG-BF) and bufalin-loaded RGD targeted PEGylated liposome (L-RGD-PEG-BF) were successfully developed with homogeneous particle size and sufficient physical stability in 30 days. The entrapment efficiency (EE) and drug loading efficiency (DL) of bufalin in these liposomes were about 85.4–90.6% and 6.0–6.6%, respectively. The morphologies of these liposomes were determined as uniquely recognizable phospholipid bilayers of the vesicle membrane by the measurements of transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). L-BF, L-PEG-BF and L-RGD-PEG-BF exhibited improved anticancer efficacy compared to free bufalin. Moreover, L-RGD-PEG-BF showed higher inhibition on the proliferation of A549 cells than the other two non-targeted bufalin liposomes in cytotoxicity study, and the growth inhibition concentration (IC50) of L-RGD-PEG-BF (8.62 ± 0.74 ng/mL) was much lower than pure bufalin (20.37 ± 2.31 ng/mL). Both confocal and apoptosis assay indicated that L-RGD-PEG-BF was easier to be taken into cancer cells than non-targeted bufalin liposomes. Therefore, L-RGD-PEG-BF is expected to be an effective drug carrier for bufalin delivery in tumor treatment.