PMID- 33069712
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 110
IP  - 3
DP  - 2021 Mar
TI  - Characterization of Aggregated Antibody-Silicone Oil Complexes: From Perspectives 
      of Morphology, 3D Image, and Fcgamma Receptor Activation.
PG  - 1189-1196
LID - S0022-3549(20)30614-6 [pii]
LID - 10.1016/j.xphs.2020.10.022 [doi]
AB  - Pre-filled syringes (PFS) have been in widespread use as an administration device 
      for therapeutic antibodies in recent decades. Generally, the inner barrel and 
      syringe of PFS are coated with silicone oil (SO) for lubrication. Multiple 
      studies have focused on the fact that the SO adsorbs denatured antibody 
      molecules, and induces antibody aggregation. Aggregated antibodies are recognized 
      as a potential risk for evoking immunogenic responses in patients. The 
      characteristics of the aggregated antibody-SO complexes, including their 
      concentration, population, shape, three-dimensional (3D) image, and Fcgamma Receptors 
      (FcgammaRs) activation have been obscurely acknowledged so far. In the present work, 
      we prepared aggregated antibody-SO complexes by agitation and analyzed using 
      multifaceted techniques such as flow imaging, confocal fluorescence microscopy, 
      and cell-based assays for FcgammaRs activation. The results emphasized that the SO 
      accelerates the increase in sub-visible particles and antibody aggregation. The 
      confocal fluorescence microscopy analysis revealed the high-resolution 3D images 
      of aggregated antibody-SO complexes. The FcgammaRs reporter cell assay clarified that 
      the pre-mixed and agitated Ab + SO have higher FcgammaRs activation capability 
      compared to the agitated Ab. Overall, this study advances the view that SO has an 
      effect to increase the risk of agitation-induced aggregated antibody particles.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kiyoshi, Masato
AU  - Kiyoshi M
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Kawasaki, Kanagawa 210-9501, Japan. Electronic address: 
      m.kiyoshi@nihs.go.jp.
FAU - Tada, Minoru
AU  - Tada M
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Kawasaki, Kanagawa 210-9501, Japan.
FAU - Shibata, Hiroko
AU  - Shibata H
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Kawasaki, Kanagawa 210-9501, Japan.
FAU - Aoyama, Michihiko
AU  - Aoyama M
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Kawasaki, Kanagawa 210-9501, Japan.
FAU - Ishii-Watabe, Akiko
AU  - Ishii-Watabe A
AD  - Division of Biological Chemistry and Biologicals, National Institute of Health 
      Sciences, Kawasaki, Kanagawa 210-9501, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201015
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Receptors, IgG)
RN  - 0 (Silicone Oils)
SB  - IM
MH  - Antibody Formation
MH  - Humans
MH  - Lubrication
MH  - *Receptors, IgG
MH  - *Silicone Oils
MH  - Syringes
OTO - NOTNLM
OT  - Biopharmaceuticals
OT  - Confocal fluorescence microscopy
OT  - FcgammaR activation
OT  - Silicone oil
OT  - Therapeutic antibody
EDAT- 2020/10/19 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/10/18 20:24
PHST- 2020/07/07 00:00 [received]
PHST- 2020/10/06 00:00 [revised]
PHST- 2020/10/07 00:00 [accepted]
PHST- 2020/10/19 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/10/18 20:24 [entrez]
AID - S0022-3549(20)30614-6 [pii]
AID - 10.1016/j.xphs.2020.10.022 [doi]
PST - ppublish
SO  - J Pharm Sci. 2021 Mar;110(3):1189-1196. doi: 10.1016/j.xphs.2020.10.022. Epub 
      2020 Oct 15.