Biomedical Engineering Reference
In-Depth Information
Fig. 10 Multifunctional solid biodegradable PLGA nanoparticles attached to several moieties
such as T-cell antibodies, magnetic resonance contrast agent (biotin-BSA-Gd-DTPA) and
encapsulated immunosuppressive drug (doxorubicin). (Adapted from [
48
])
1 h for long-chain (5,000 Da) methoxy-PEG QDs. These coatings determined the
pattern of in vivo tissue localization, with retention of some QDs occurring up to
4 months.
PEGylation of nanospheres can be carried out either via a simple adsorption of
PEG chains onto the nanoparticles or by a covalent linkage of PEG chains with
poly(alkyl cyanoacrylate) (PACA) polymers. The adsorption approach is not pref-
erable since there is no covalent linkage and is not really suitable enough for in vivo
applications. It has been demonstrated that these kinds of assemblies (PACA
nanoparticles on which poloxamer 388 or poloxamine 908 was adsorbed) are
not stable during in vivo administration, resulting in a loss of coating, and
have no significant influence on the biodistribution pattern [
52
]. Biodegradable
nanoparticles show an increased residence time in blood vessels that could over-
come the post-treatment accumulation of the free drug. In addition, sterilization of
the polymeric nanoparticles by membrane filtration is feasible, which offers a great
advantage.
Some advantages of PEG surface modification are: (1) water solubility, (2) high
mobility in solution, (3) lack of toxicity and immunogenicity, (4) ready clearance
from the body, and (5) altered distribution in the body.
PEG polymer has to be suitably functionalized at one or both terminals. PEGs
that are activated at each terminus with the same reactive moiety are known as
“homobifunctional.” If the functional groups present are different, then the PEG
derivative is referred as “heterobifunctional” or “heterofunctional.” Chemically
activated PEG polymer derivatives are used to attach the PEG to the desired
molecule or ligand.
Two ways of linking the PEG molecules are: (1) PEG derivatives are obtained by
reacting the PEG polymer with a group that is reactive with hydroxyl groups, e.g.,
anhydride, acid chloride, chloroformate or carbonate; and (2) attachment of func-
tional groups such as aldehydes, esters, amides etc. with the PEG polymer.
The heterobifunctional PEGs are very useful in linking two entities in cases
where a hydrophilic, flexible, and biocompatible spacer is needed. Preferred end
groups for heterobifunctional PEGs are maleimides, vinyl sulfones, pyridyl
disulfides, amines, carboxylic acids, and
N
-hydroxysuccinimide (NHS) esters.
