Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 310

response to liposomes involving specific immunity is exemplified by
PEGylated nanoliposome-induced transient IgM production, which
causes accelerated blood clearance (ABC). Immunosuppression
occurs mostly with anticancer and antifungal liposomes. This chapter
updates the information on CARPA, accelerated blood clearance (ABC
phenomenon), and immunosuppression; highlights their common
and specific causes; and discusses their mechanisms.
11.1 Introduction
Today, 46 years after the discovery of liposomes [10, 25], 34 years
after their first injection in man against Gaucher's disease [12] and
with more than 10 liposomal drugs in clinical use [63, 92, 93], the
adverse eff ects of liposomes on the immune system represent a
relatively poorly explored territory within ”liposomology.”
This, however, will likely change in the near future as the rising
number of advanced liposome-based drugs reach in vivo testing.
These advanced nano-liposomes include targeting ligands and/
or proteins or nucleic acids as the active ingredient, making the
particles more complex than the currently approved liposomal
drugs. Therefore, they may carry increased risk of recognition by the
immune system as foreign. Unless we understand the cellular and
molecular processes underlying the ensuing protective/defensive
response, the absence of adverse eff ects — a unique asset of simple
liposomes — will probably become the exception rather than the
rule. The immunological eff ects of liposomes will extend its present
focus, from the use of liposomes as vaccines, to mapping an uncharted
network of hypersensitivity and immunogenicity reaction pathways.
As the safety of medicinal nanoparticles comes more to the fore,
reactogenicity and immunogenicity testing may join the list of toxicity
and QC assays required by regulatory agencies. A deeper insight into
the fine immunomodulatory eff ects of such complex nano-particles
may also lead to a need to revise our views on immune suppression,
not as a side eff ect but as contributor to therapeutic benefit. This
seems to be the case with Doxil, the first nano-drug approved by the
US FDA, which is the subject of Chapter 12.
It looks like future nano-particle based drugs will have a less
smooth path of safety clearance compared with what we used to have
so far, a toll we may need to pay for nursing small-molecular-weight