Effect of Kupffer cells depletion on ABC phenomenon induced by Kupffer cells-targeted liposomes

In this study, the correlation between Kupffer cells (KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside (APM) lipid derivative DSPE-PEG2000-APM (DPM), and 4-aminophenyl-β-L-fucopyranoside (APF) lipid derivative DSPE-PEG2000-APF (DPF) were conjugated and modified on alendronate sodium (AD) liposomes to specifically target and deplete KCs. The dual-ligand modified PEGylated liposomes (MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes (PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What's more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs....
Source: Asian Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Source Type: research