Pegylated cerasomes exhibit accelerated blood clearance in rats despite no elevation of anti-PEG IgM and IgG antibodies.

PEGylated nanocarriers could trigger the "accelerated blood clearance (ABC) phenomenon" upon repeated administration. Cerasomes, which are liposomes reinforced with a robust organosiloxane network, exhibit remarkably higher physicochemical stability and more controlled release behavior than traditional liposomes. This study aimed to explore the occurrence of ABC in PEGylated cerasomes, which, to our knowledge, has not been previously examined. The effects of dosing intervals (3, 5, 7, and 14 days) and surface charge were also investigated. Ag2S quantum dots were encapsulated for in vivo tracking of the vesicles, and IgM and IgG levels, as well as complement activity, were measured as biomarkers for the ABC phenomenon. Results revealed that PEGylated cerasomes can induce a notable ABC phenomenon, particularly at a 3-day dosing interval, whereas PEGylated liposomes (serving as the positive control) peaked at a 5-day interval. ABC was no longer observable at a 14-day interval, suggesting a shorter persistence for cerasomes compared to liposomes. The ABC index for negatively charged cerasomes was significantly lower than that for neutral cerasomes (0.129 vs. 0.766), underscoring the impact of surface charge on ABC intensity. Interestingly, anti-PEG IgM levels were undetectable in cerasomes despite the pronounced ABC phenomenon, indicating that the mechanism for cerasome ABC may differ from that of PEGylated liposomes. In addition, no anti-PEG IgG secretion was observed in any of the treated groups. Since the ABC of cerasomes was accompanied by significant complement activity, it could be suggested that the ABC of cerasomes was intensified through an antibody-independent complement activation pathway.