VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 209

charge should not change dramatically. This phenomenon has been found to
hold true for other proteins, liposomes, and nano- and microspheres as well
(Levchenko

et al ., 2002; Moore et al ., 1977; Roser et al ., 1998; Wachsmuth &

Klingmuller, 1978; Yamasaki ., 2002).

The impact on plasma circulation is not solely dependent on the surface
charge; materials properties derived from the ligands attached will also
impact the

et al

properties. For example, if PEG chains are attached to
Lys side chains, the properties of the PEG typically outweigh the charge
effect and longer circulation times are achieved (see Section 8.1.2).
It is difficult to precisely predict the

in vivo

properties of a particular
formulation; each formulation generated must be evaluated in detail prior
to its clinical use.

in vivo

8.1.2 PEGylaion - A Strategy to Reduce Biospeciic Interacions
and Immunogenicity, and Increase Plasma Circulaion Time

Figure 8.1 Structure of polyethylene glycol (PEG).

For certain applications in nanomedicine such as imaging or drug
delivery, immunogenicity may be regarded as an undesired side effect.
Strategies that overcome or reduce the immunogenic properties of VNPs
have been developed; the most prominent technique is the attachment
of polyethylene glycol (PEG) to biomolecules or nanomaterials, termed
PEGylation .

Polythylene glycol (Fig. 8.1) is a non-charged, highly hydrophilic polymer.
PEG is non-toxic and has been approved for use in humans by the U.S. Food
& Drug Administration (FDA). Increasingly being used for pharmaceuticals
and other biomedical applications, PEGylation efficiently reduces or blocks
biospecific interactions, increases solubility and stability, increases plasma
circulation time, and reduces immunogenicity. PEGylation has been applied
to a variety of nanomaterials including liposomes, carbon nanotubes,
and dendrimers (reviewed in Harris & Chess, 2003; Roberts

et al ., 2002;

Wattendorf & Merkle, 2008).
PEGylation can be achieved using a range of bioconjugation methods
(see Chapter 4). PEG chains may be activated with a range of functionalities
to allow covalent coupling to the desired molecule or material. Modified PEG
chains are commercially available, as well as bivalent PEG molecules that
allow interlinking of different functionalities.