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The following administration causes drug–IgM binding, complement system activation and liposome capturing by macrophages.24 This phenomenon is a very fast immune reaction that occurs in 10 min after first intravenous injection.25 Moreover, the spleen seems to be the main producer of anti-PEG IgM.26 It should be noted that secretion of IgM antibodies is dose dependent and that the immune response activation rate is higher when triggered by nucleic acids.27 Nevertheless, the third and later administrations of PEG-liposomes do not cause such a strong effect due to MPS cell saturation

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