In-vivo disposition characteristics of PEG niosome and its interaction with serum proteins

Three different nonionic surfactants (Brij 72, Span 20 and Tween 60) were used to prepare various naked and PEG niosomes. In-vivo study demonstrated that PEGylation dramatically increased the AUC and decreased the affinity to the liver of Brij 72 and Span 20 niosomes in rats. Liver perfusion experiments suggested that the hepatic uptake of naked Brij 72 and Span 20 niosomes could mainly be ascribed to the receptor-mediated uptake, while PEGylation of these niosomes could diminish the receptor-mediated hepatic disposition. Evaluation of serum proteins associated with niosomes revealed that PEGylation of these niosomes significantly reduced the association of serum proteins with them, including typical opsonins such as IgG and C3. On the other hand, in the case of Tween 60 niosomes, naked Tween 60 niosome showed large AUC and its PEGylation did not show any additional effect on the in-vivo pharmacokinetics. Furthermore, PEGylation of Tween 60 niosome did not significantly affect the hepatic disposition or the association of serum proteins with Tween 60 niosome. These results demonstrated that niosomes would exhibit distinct in-vivo disposition characteristics depending on the physicochemical properties of surfactants used and that PEGylation of niosomes with adequate compositions would be a powerful tool to improve their in-vivo behavior.