TY - JOUR
T1 - Evasion of the accelerated blood clearance phenomenon by polysarcosine coating of liposomes
AU - Son, Kon
AU - Ueda, Motoki
AU - Taguchi, Kazuaki
AU - Maruyama, Toru
AU - Takeoka, Shinji
AU - Ito, Yoshihiro
N1 - Funding Information:
This work was financially supported by the Japan Society for the Promotion of Science , a Grant-in-Aid for Scientific Research (S) from KAKENHI 22220009 , a Grant-in-Aid for Scientific Research (A) from KAKENHI 15H01810 , and a Grant-in-Aid for Early-Career Scientists from KAKENHI 18K15334 . TEM measurements were supported by the Materials Characterization Support Unit , RIKEN CEMS. We thank the Edanz Group ( www.edanzediting.com/ac ) for editing a draft of this manuscript.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/6/10
Y1 - 2020/6/10
N2 - Using polyethylene glycol (PEG) to functionalize liposomes improves their stealth properties and stability in blood. However, PEG is known to induce the accelerated blood clearance (ABC) phenomenon, which occurs for multiple doses owing to anti-PEG IgM being produced after the initial injection. In this study, as an alternative to PEG, polysarcosine (PSar) was selected owing to its low antigenicity and its highly dense chains with controllable lengths, similar to PEG. Furthermore, we directly evaluate the potential of PSar for avoiding the ABC phenomenon by comparing PSar with PEG on the same liposome platform, which has similar physicochemical properties such as hydrophobic region, membrane fluidity, and size. PEG- and PSar-liposomes were prepared and characterized for comparison. PSar-liposomes showed similar physicochemical properties to PEG-liposomes in terms of size control, zeta potential, membrane polarity, and fluidity; however, ELISA results showed noticeably lower levels and faster production speeds of both IgM and IgG for PSar-liposomes than for PEG-liposomes. In addition, a pharmacokinetics experiment with multiple injections showed that PSar-PE coating of liposomes may help to circumvent the ABC phenomenon.
AB - Using polyethylene glycol (PEG) to functionalize liposomes improves their stealth properties and stability in blood. However, PEG is known to induce the accelerated blood clearance (ABC) phenomenon, which occurs for multiple doses owing to anti-PEG IgM being produced after the initial injection. In this study, as an alternative to PEG, polysarcosine (PSar) was selected owing to its low antigenicity and its highly dense chains with controllable lengths, similar to PEG. Furthermore, we directly evaluate the potential of PSar for avoiding the ABC phenomenon by comparing PSar with PEG on the same liposome platform, which has similar physicochemical properties such as hydrophobic region, membrane fluidity, and size. PEG- and PSar-liposomes were prepared and characterized for comparison. PSar-liposomes showed similar physicochemical properties to PEG-liposomes in terms of size control, zeta potential, membrane polarity, and fluidity; however, ELISA results showed noticeably lower levels and faster production speeds of both IgM and IgG for PSar-liposomes than for PEG-liposomes. In addition, a pharmacokinetics experiment with multiple injections showed that PSar-PE coating of liposomes may help to circumvent the ABC phenomenon.
KW - Accelerated blood clearance (ABC) phenomenon
KW - Anti-PEG IgM
KW - Liposome
KW - Polyethylene glycol (PEG)
KW - Polysarcosine
KW - Repeated administration
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U2 - 10.1016/j.jconrel.2020.03.022
DO - 10.1016/j.jconrel.2020.03.022
M3 - Article
C2 - 32194174
AN - SCOPUS:85082166171
SN - 0168-3659
VL - 322
SP - 209
EP - 216
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -