Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 316

11.4 Consequences of Immune Recognition of

Liposomes

11.4.1 Acute Hypersensitivity Reactions

11.4.1.1 Symptoms and occurrence
Acute hypersensitivity reactions (HSRs) to liposomes have been
reported from time to time, ever since 1986, the first clinical study
wherein large doses of liposomes were infused in cancer patients
[76]. All kinds of liposomes and lipid-based drugs can cause such
reactions, as follows from the large variety of vesicles reported to be
reactogenic [15, 22, 30, 32, 38-41, 70, 75]. The reported frequency
following premedication and/or other precautionary measures,
such as the extension of treatment time with very slow initial
rate of infusion, usually remains below 10% [28, 82, 84]. Without
premedication, however, HSRs were observed in 45% of patients
treated for the first time with Doxil [16]. Recommendation for ready
access to emergency equipment to treat HSRs reactions has recently
become part of the box insert of Doxil [28].
Table 11.3 categorizes the symptoms of HSRs according to organ
systems involved [80-84]. The wide range of symptoms reflects
complex and highly individual pathomechanism. Of note, death,
whenever it occurs, is mostly due to cardiac anaphylaxis, as a result
of massive anaphylatoxin (C3a, C5a) release and their impact on the
heart [84, 86].

Table 11.3 Symptoms of acute hypersensitivity (infusion) reactions*

Cardio-
vascular

Broncho-
pulmonary

Muco-
cutaneous

Neuro-
psychosomatic

Autonomic

arrhythmia apnea cyanosis back pain chills

carcinogenic
shock

bronchospasm erythema chest pain diaphoresis

edema coughing flushing chest tightness diarrhea

hypertension dyspnea rash headache dizziness

feeling of
imminent death fever

hypotension hyperventilation rhinitis

hypoxia laryngospasm swelling fright nausea