Preparation and evaluation of long circulating erythrocyte membrane-cloaked anti-cancer drug delivery system

Recently, biomimetic hybrid drug delivery systems, especially erythrocyte membrane-based drug delivery systems, have been utilized to achieve high bioavailability, and biocompatibility, in the meantime, to reduce immunogenicity and effectively evade phagocytosis of the host immune system. Here, we developed a novel drug delivery system of red blood cell membrane-derived vesicles (RDVs) cloaked poly (acrylic acid)-cystamine hydrochloride-D-alpha-tocopherol succinate (PAAssVES) nanoparticles. The PAAssVES nanoparticles were prepared via emulsification and solvent volatilization method, followed by loading of the model anti-cancer drug, sorafenib (SFN). Then RDVs and SFN-PAAssVES nanoparticles were uniformly mixed and co-extruded through polycarbonate membrane. The prepared RDV-coated nanoparticles (RDV-NPs) had good stability, with a zeta potential of - 10.7 mV and particle size of 113.5 nm. MTT assay was used to analyze the effects of RDV-NPs on cell viability in two kinds of gastric cancer cell lines BGC-823 and MKN-45. The results showed that RDV-NPs significantly decreased cell viability. In vitro drug release investigation showed that RDV-NPs had good sustained release properties and the cumulative release was 71.5% in 72 h. In pharmacokinetic studies, SD male rats' intravenous injection with RDV-NP solution showed a more smooth plasma concentration-time profile. Compared with free SFN treatment and SFN-PAAssVES group, RDV-NPs enhanced the AUC by about 4.1-fold and 2.0-fold. The MRT and t(1/2) of RDV-NPs were increased to 23.670 +/- 2.347 h and 24.450 +/- 2.652 h. Our study demonstrated the promise of using RDV-NPs as a long circulating anti-cancer drug delivery system. Graphical abstract