Biomedical Engineering Reference
In-Depth Information
functionalized. Inorganic nanoparticles, however, are generally unstable and may
be toxic in biological systems. Accordingly, surface modification is needed to
improve the biological stability and biocompatibility.
Surface modification of inorganic nanoparticles with PEG is a very useful way to
overcome this problem. For instance, thiol groups are suitable anchors on gold
nanoparticles. A variety of drugs, such as small compounds, oligonucleotides, and
proteins, have been delivered by gold nanoparticles that carry drugs co-
immobilized with thiol-PEG [
74
,
75
]. For instance, recombinant human TNF-
a
was immobilized on PEGylated colloidal gold nanoparticles [
76
] to facilitate
preferential accumulation of TNF-
a
in tumors and minimal uptake in healthy
organs. This TNF-
a
-immobilized gold nanoparticle has been evaluated in a Phase
I clinical trial [
77
]. Our group has investigated the stabilization of nanoparticles
by block copolymers possessing PEG as one of the segments. For example,
PEG-
b
-poly[2-(
N,N
-dimethylamino)ethyl methacrylate] significantly improves
the stabilization of gold nanoparticles under physiological conditions [
78
,
79
].
Multi-anchoring of amino groups in the poly[2-(
N,N
-dimethylamino)ethyl methac-
rylate] segment strongly improves adsorption efficiency. Luminescent nanoparticles
have also been modified by several block copolymers [
80
,
81
].
5 Conclusions and Future Prospects
Since PEGylation of proteins was first reported in the 1970s, extensive research on
PEGylation technology and pharmaceutical development of PEGylated molecules
has been conducted. A variety of molecules, including small organic molecules,
proteins, antibody fragments, and nanoparticles have been modified with PEG.
Currently, 11 PEGylated drugs have been marketed, and many other PEGylated
drugs are in clinical trials. In recent years, the success rate for bringing new drugs to
market has been decreasing [
82
]. One of the reasons for this is that the FDA is
highly focused on the safety of new drugs. In this regard, PEGylation is very useful
because PEG is categorized as “generally regarded as safe” (GRAS) by the FDA.
Although there are potential concerns regarding non-degradability, product hetero-
geneity, and accumulation of large linear PEG chains in the liver [
22
], PEG
provides substantial benefits, such as reduced immunogenicity and antigenicity of
the drug. As in the cases of PEG-INTRON, Neulasta, and Doxil, emerging drugs
can be developed by PEGylation of previously commercialized non-PEGylated
drugs. By further development of cost-effective PEGylation technologies that
enable more controlled release of PEG from the drug and site-specific modifications
to deliver homogeneous products, the market of PEGylated drugs will continue
to grow.
