Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 312

immunogenicity, as antigens may remain unrecognized or can induce
immune suppression (tolerance).

Table 11.1 Types of liposome-induced immune changes according to the
time of onset and duration

Type of
change

Example and
reference

Time of onset Duration

Stimulation Immediate
(within seconds
to minutes)

Hypersensitivity
(infusion) reactions
caused by liposomes
[84-86, 89]

Minutes to
hours

Delayed (within
hours)
Late (within days
to months)

Weeks to years Immunity to
liposomal antigens,
e.g. influenza or
hepatitis B [2, 13]

Inhibition Short term Hours to days Liposomal

alendronate [21]

Long term Days to months Doxil-induced

immunosuppression
[1, 37, 79]

To date, two aspects of the impact of liposomes on the immune
system were explored: first, in the 1970s, the late-onset, long-lasting
immunogenic properties of phospholipid bilayers were recognized
and utilized as antigen carriers and adjuvants. Since then, numerous
vaccine candidates have reached advanced clinical trials, and
two products, an influenza (Inflexal ® V) and a hepatitis A vaccine
(Epaxal ® ) have reached the market; both are based on influenza
virus-like liposomes (“immune-potentiating reconstituted influenza
virosomes”). Another proteoliposome-based hepatitis-B vaccine in
current testing worldwide is based on yeast derived or mammalian
recombinant, 22 nm-hepatitis B surface antigen particles carried by
multilamellar liposomes [26, 27].
The second “bad” aspect of immune stimulation by liposomes, i.e.,
the rise of immune responses with adverse consequences, emerged
only some 20 years later, after clinical studies started with liposome-
based antifungal and anticancer drugs (Ambisome and Doxil) [11,
18, 34, 36, 66, 77]. The rest of the chapter focuses only on the latter,