PMID- 37355210
OWN - NLM
STAT- MEDLINE
DCOM- 20230821
LR  - 20230822
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 360
DP  - 2023 Aug
TI  - Anti-PEG IgM production induced by PEGylated liposomes as a function of 
      administration route.
PG  - 285-292
LID - S0168-3659(23)00400-5 [pii]
LID - 10.1016/j.jconrel.2023.06.027 [doi]
AB  - Modifying the surface of nanoparticles with polyethylene glycol (PEG) is a 
      commonly used approach for improving the in vitro stability of nanoparticles such 
      as liposomes and increasing their circulation half-lives. We have demonstrated 
      that, in certain conditions, an intravenous (i.v.) injection of PEGylated 
      liposomes (PEG-Lip) induced anti-PEG IgM antibodies, which led to rapid clearance 
      of second doses in mice. SARS-CoV-2 vaccines, composed of mRNA-containing 
      PEGylated lipid nanoparticles, have been widely administered as intramuscular 
      (i.m.) injections, so it is important to determine if PEGylated formulations can 
      induce anti-PEG antibodies. If the favorable properties that PEGylation imparts 
      to therapeutic nanoparticles are to be widely applicable this should apply to 
      various routes of administration. However, there are few reports on the effect of 
      different administration routes on the in vivo production of anti-PEG IgM. In 
      this study, we investigated anti-PEG IgM production in mice following i.m., 
      intraperitoneal (i.p.) and subcutaneous (s.c.) administration of PEG-Lip. PEG-Lip 
      appeared to induce anti-PEG IgM by all the tested routes of administration, 
      although the lipid dose causing maximum responses varied. Splenectomy attenuated 
      the anti-PEG IgM production for all routes of administration, suggesting that 
      splenic immune cells may have contributed to anti-PEG IgM production. 
      Interestingly, in vitro experiments indicated that not only splenic cells but 
      also cells in the peritoneal cavity induced anti-PEG IgM following incubation 
      with PEG-Lip. These observations confirm previous experiments that have shown 
      that measurable amounts of PEG-Lip administered i.p., i.m. or s.c. are absorbed 
      to some extent into the blood circulation, where they can be distributed to the 
      spleen and/or peritoneal cavity, and are recognized by B cells, triggering 
      anti-PEG IgM production. The results obtained in this study have important 
      implications for developing efficient PEGylated nanoparticular delivery system.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Takata, Haruka
AU  - Takata H
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
FAU - Shimizu, Taro
AU  - Shimizu T
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
FAU - Yamade, Rina
AU  - Yamade R
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
FAU - Elsadek, Nehal E
AU  - Elsadek NE
AD  - Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig 
      University, Zagazig 44519, Egypt.
FAU - Emam, Sherif E
AU  - Emam SE
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan; 
      Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig 
      University, Zagazig 44519, Egypt.
FAU - Ando, Hidenori
AU  - Ando H
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
FAU - Ishima, Yu
AU  - Ishima Y
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan.
FAU - Ishida, Tatsuhiro
AU  - Ishida T
AD  - Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical 
      Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan. 
      Electronic address: ishida@tokushima-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230629
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 0 (Liposomes)
RN  - 0 (COVID-19 Vaccines)
RN  - 0 (Immunoglobulin M)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - *Polyethylene Glycols
MH  - Liposomes
MH  - COVID-19 Vaccines
MH  - Immunoglobulin M
MH  - *COVID-19
MH  - SARS-CoV-2
OTO - NOTNLM
OT  - Administration route
OT  - Anti-PEG IgM
OT  - PEGylated nanoparticles
OT  - Polyethylene glycol (PEG)
OT  - T cell independent (TI) antigen
COIS- Declaration of Competing Interest None.
EDAT- 2023/06/25 01:08
MHDA- 2023/08/21 06:42
CRDT- 2023/06/24 19:17
PHST- 2023/03/12 00:00 [received]
PHST- 2023/06/04 00:00 [revised]
PHST- 2023/06/18 00:00 [accepted]
PHST- 2023/08/21 06:42 [medline]
PHST- 2023/06/25 01:08 [pubmed]
PHST- 2023/06/24 19:17 [entrez]
AID - S0168-3659(23)00400-5 [pii]
AID - 10.1016/j.jconrel.2023.06.027 [doi]
PST - ppublish
SO  - J Control Release. 2023 Aug;360:285-292. doi: 10.1016/j.jconrel.2023.06.027. Epub 
      2023 Jun 29.