Chapter 20
Immune Response to PEGylated
Nanomedicines: Impact of IgM
Response
Amr S. Abu Lila and Tatsuhiro Ishida
Abstract PEGylation is one of the most commonly applied approaches to realize
the stealthiness of the conjugated nanomaterials in the systemic circulation.
Nevertheless, despite the fact that Polyethylene glycol (PEG) is biologically inert, a
mounting body of evidences has confirmed the presence of anti-PEG antibodies
(anti-PEG Abs) that trigger an immunogenic response against PEG conjugates in a
manner wherein PEG acts as a hapten. Since anti-PEG Abs are correlated with the
accelerated clearance of subsequently administered doses of PEGylated nanocarriers, via a phenomenon known as “accelerated blood clearance” phenomenon, the
existence of anti-PEG Abs has been claimed for the reduced efficiency of
PEGylated therapeutics and/or development of severe adverse effects. Accordingly,
careful monitoring for anti-PEG Abs is necessary prior to and throughout a course
of treatment with PEGylated therapeutics. Furthermore, strategies to avert the
challenges of PEG-specific immunity are needed with a deeper understanding of the
mechanism of anti-PEG immunity.
20.1 Introduction
PEGylation, covalent coupling of the hydrophilic polymer polyethylene glycol
(PEG) to nanocarriers-based and/or protein therapeutics, is one of the commonly
applied approaches to realize the stealthiness of the conjugated nanomaterials in the
A. S. Abu Lila Á T. Ishida (&)
Department of Pharmacokinetics and Biopharmaceutics, Institute of Medical
Biosciences, Tokushima University, 1-78-1, Sho-Machi, Tokushima 770-8505, Japan
e-mail: ishida@tokushima-u.ac.jp
A. S. Abu Lila
Department of Pharmaceutics and Industrial Pharmacy,
Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
A. S. Abu Lila
Department of Pharmaceutics, College of Pharmacy, Hail University,
Hail 81442, Saudi Arabia
© Springer International Publishing AG, part of Springer Nature 2018
D. S. Lee (ed.), Radionanomedicine, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-67720-0_20
371
Immune Response to PEGylated
Nanomedicines: Impact of IgM
Response
Amr S. Abu Lila and Tatsuhiro Ishida
Abstract PEGylation is one of the most commonly applied approaches to realize
the stealthiness of the conjugated nanomaterials in the systemic circulation.
Nevertheless, despite the fact that Polyethylene glycol (PEG) is biologically inert, a
mounting body of evidences has confirmed the presence of anti-PEG antibodies
(anti-PEG Abs) that trigger an immunogenic response against PEG conjugates in a
manner wherein PEG acts as a hapten. Since anti-PEG Abs are correlated with the
accelerated clearance of subsequently administered doses of PEGylated nanocarriers, via a phenomenon known as “accelerated blood clearance” phenomenon, the
existence of anti-PEG Abs has been claimed for the reduced efficiency of
PEGylated therapeutics and/or development of severe adverse effects. Accordingly,
careful monitoring for anti-PEG Abs is necessary prior to and throughout a course
of treatment with PEGylated therapeutics. Furthermore, strategies to avert the
challenges of PEG-specific immunity are needed with a deeper understanding of the
mechanism of anti-PEG immunity.
20.1 Introduction
PEGylation, covalent coupling of the hydrophilic polymer polyethylene glycol
(PEG) to nanocarriers-based and/or protein therapeutics, is one of the commonly
applied approaches to realize the stealthiness of the conjugated nanomaterials in the
A. S. Abu Lila Á T. Ishida (&)
Department of Pharmacokinetics and Biopharmaceutics, Institute of Medical
Biosciences, Tokushima University, 1-78-1, Sho-Machi, Tokushima 770-8505, Japan
e-mail: ishida@tokushima-u.ac.jp
A. S. Abu Lila
Department of Pharmaceutics and Industrial Pharmacy,
Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
A. S. Abu Lila
Department of Pharmaceutics, College of Pharmacy, Hail University,
Hail 81442, Saudi Arabia
© Springer International Publishing AG, part of Springer Nature 2018
D. S. Lee (ed.), Radionanomedicine, Biological and Medical Physics,
Biomedical Engineering, https://doi.org/10.1007/978-3-319-67720-0_20
371