Study on the protection of dextran on erythrocytes during drug loading

In comparison to other carriers, erythrocytes (red blood cells, RBCs) hold the advantages of unmatched long circulation, biocompatibility and biodegradability. However, because of the defects in RBCs carriers caused by the drug loading process, the biological activities of drug-loaded RBCs are worse than those of natural RBCs (NRBCs). We aim to study the protective effect of dextran on the activity of drug-loaded RBCs. Different molecular weights of dextran were selected and added to a hypotonic drug solution to prepare drug-loaded RBCs by the hypotonic preswelling method. Water-soluble betamethasone sodium phosphate (BSP) and fat-soluble artesunate (AS) were selected as model drugs. The results showed that the addition of dextran with a molecular weight of 40 kDa and a concentration of 10 % could significantly increase the Na⁺/K⁺-ATPase activity, improve the drug loading amount and lower the phosphatidylserine eversion rate. Moreover, it maintained a similar osmotic fragility to NRBCs and exhibited no effect on the morphological structure of drug-loaded RBCs. Laser confocal results showed tight covering of dextran over RBCs, which could explain the protective effects. The addition of dextran increased the activity of drug-loaded RBCs without affecting their in vivo circulation (at least nine days). In conclusion, 10 % dextran with a weight of 40 kDa displayed a significant protective effect on the bioactivity of drug-loaded RBCs, which could be expected to be a better way to facilitate hydrophobic and hydrophilic drug loading by RBCs.