VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 207

VNPs derived from plant viruses and phages are less likely to interact
specifically with the mammalian system and therefore less likely to
cause potential toxic side effects. For

Cowpea mosaic virus (CPMV), it was

shown that, even up to dosages of 10 CPMV particles per kilogram body

weight, no apparent toxic side effects were observed (Singh

16

., 2007).
Animals injected intravenously with 1, 10, and 100 mg/kg CPMV did
not show any apparent clinical signs, or evidence of toxicity (Singh

et al

.,
2007). These findings were in good agreement with studies using CCMV,
where

et al

(CCMV)-injected animals did not show
any clinical symptoms and did not have any histological pathology (Kaiser
et al

Cowpea chlorotic mottle virus

., 2007).
VNPs are immunogenic materials, and it was suggested that they are
eliminated via B-lymphocytes (these cells are part of the humoral immune
system, as opposed to the cell-mediated immune system). In the case of
some VNPs (CPMV, T7, and Q

b

), it has been shown that administration
leads to a transient increase in the B-cell numbers; however, animals
recover from this response within a few days, suggesting clearance of the
VNPs (Gatto

et al ., 2004; Singh et al ., 2007; Srivastava et al ., 2004). It was

indicated that CPMV particles persist for at least 3 days (Rae ., 2005). In

contrast, CCMV particles are nearly completely eliminated within 24 h after
administration (Kaiser

et al

et al ., 2007). Data from longer-term studies have not

been reported yet.

8.1.2 Plasma Clearance, Bioavailability, and Biodistribuion

Pharmacokinetics and tissue biodistribution are important factors to evaluate
in vivo

, and characteristics such as particle size, surface charge, and alteration
play a crucial role. It is important to find the right balance between tissue
penetration and systemic clearance. Longer circulation times allow greater
specificity and better accumulation in the target tissue; however, more rapid
clearance might be desired to reduce toxic side effects or background for
imaging (Thurber ., 2008).

Both CPMV and CCMV have broad biodistribution and were detected in
a wide variety of tissues throughout the body with no apparent toxic effects
(Kaiser

et al

et al ., 2007; Rae et al ., 2005). CPMV particles mostly accumulated

in liver and spleen (Singh et al ., 2007). This distribution is similar to

observations made using Q .,

2008). A different pattern was observed with CCMV; CCMV particles were
mostly found in the thyroid as well as in liver, spleen, bladder, and salivary
gland (Kaiser

b

and M13 (Molenaar et al ., 2002; Prasuhn et al

., 2007). Uptake and accumulation of VNPs in organs with
filtration function, such as liver and spleen, were expected. These organs are

et al