Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 317

Cardio-
vascular

Broncho-
pulmonary

Muco-
cutaneous

Neuro-
psychosomatic

Autonomic

myocardial
infarction

pulmonary
infiltration

urticaria panic sweating

respiratory
distress

tachycardia rigors vomiting

ventricular
fibrillation

shortness of
breath

tightness of
chest, throat

wheezing

*Compilation of symptoms was based on the adverse events reports in the box labels
of liposomes and other reactogenic nanomedicines.

11.4.1.2 Complement activation by liposomes as an

underlying mechanism of hypersensitivity reactions

Features of C activation and CARPA . Since the recognition of
C activation by liposomes in 1968/69 [4, 47, 48, 56], numerous
studies analyzed this phenomenon in vitro and in vivo under
various conditions. As reviewed previously [80-84], the outcomes
of these experiments were highly variable as a consequence of the
substantial diff erences in vesicles studied, animal models, serum
sources and experimental conditions. Nevertheless, numerous
common and basic features of the phenomenon have been uncovered
both in vitro [8, 14, 17, 20, 33, 42, 43, 45, 47, 56, 64, 67, 69, 71, 72,
74, 80, 81, 83, 84, 90] and in vivo [85-89], summarized in Tables 11.4
and 11.5, respectively.
Mechanisms involved in C activation and CARPA . In commenting
on the mechanisms of some of the eff ects listed in Table 11.4,
surface charge is perhaps the best known enhancer of C activation
induced by nanoparticles and liposomes. A closer scrutiny of the
phenomenon at atomic level revealed that the oxygen moiety of
the mPEG-phospholipid is responsible for enhanced C activation,
at least for the case of mPEGylated dipalmitoylphosphatidylcholine
(DPPC) liposomes [68]. The evidence included the lack of activation
by non-PEGylated vesicles and the inhibition of C activation by
methylation of the oxygen moiety on mPEG-DPPE phosphate [68].
In other studies it was further shown that the C activating negative
charge needs to be part of conventional anionic phospholipids, as
carboxylic acid-modified vesicles having the same surface charge