title: Interaction kinetics of serum proteins with liposomes and their effect on phospholipase-induced liposomal drug release.
abstract: We used surface plasmon resonance (SPR) to measure the affinity and kinetics of the interaction between serum proteins and both conventional and PEGylated liposomes. The effect of the interactions on secretory phospholipase A2 (sPLA2)-induced release of a model drug from liposomes was also assessed. SPR analysis of 12 serum proteins revealed that the mode of interaction between serum proteins and liposomes greatly varies depending on the type of protein. For example, albumin bound to liposomes at slower association/dissociation rates with higher affinity and prevented sPLA2-induced drug release from PEGylated liposomes. Conversely, fibronectin bound at faster association/dissociation rates with lower affinity and demonstrated little impact on the drug release. These results indicate that the effect of serum proteins on sPLA2 phospholipid hydrolysis varies with the mode of interaction between proteins and liposomes. Understanding how the proteins interact with liposomes and impact sPLA2 phospholipid hydrolysis should aid the rational design of therapeutic liposomal formulations.
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan. Electronic address: h-shibata@nihs.go.jp.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shibata
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Izutsu
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haishima
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanishi
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan.
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.affiliation: National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo158-8501, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Goda
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D065546:Drug Liberation; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011485:Protein Binding; D020349:Surface Plasmon Resonance
chemical_list: D001798:Blood Proteins; D008081:Liposomes; D011092:Polyethylene Glycols; D054467:Phospholipases A2
keywords: Drug release; Liposomes; Phospholipase A2; Serum protein; Surface plasmon resonance