Biomedical Engineering Reference
In-Depth Information
The presence of Blood-Brain Barrier (BBB) prevents easy delivery of most of
the medicines and drugs such as doxorubicin, tubocurarine, and dalargin. Cova-
lently attached apolipoproteins (mainly apoE, apoA-I, and apoB-100) enhance
the nanoparticle transport across the blood-brain barrier [
2
]. Therefore, researchers
are trying to find suitable surface treatments to encourage the adsorption of
apolipoproteins in the protein corona for brain-targeting applications. Stabilization
of solid lipid NPs (polybutylcyanoacrylate) by polysorbates enhanced the crossing
of these NPs through the BBB by preferential adsorption of apolipoprotein E
(Fig.
3.3
). It was noticed that among polysorbate
X
with
X
¼
20, 40, 60, and
80, polysorbate 80 showed the highest potential for brain-targeted drug delivery
[
33
]. The role of poloxamer polymers and poloxamine 908 as stabilizers of solid
lipid nanoparticles has also been investigated, and it was found that the shorter the
poly(ethylene oxide) chain, the larger adsorption of apolipoprotein E [
34
].
This idea that specific proteins in the protein corona can be used for targeting
goals can be extended to attach those specific proteins on NPs. Albumin is one of
the major constituent of protein plasma for most of the NPs when they come into
contact with blood plasma. However, pre-binding with albumin can be employed
for targeting objectives. An example of an available drug in the market are
Abraxane
which is the paclitaxel with albumin attached to its surface. The
nanoparticle albumin-bound paclitaxel (
nab
-paclitaxel) showed superior tumor
targeting, enhanced tumor uptake, and decreased toxicity in comparison with
solvent-based paclitaxel [
2
,
35
]. The nanoparticle albumin-bound drugs which are
abbreviated as
nab
technology is receiving more research interest to be extended to
other drugs such as docetaxel for solid tumor targeting and rapamycin as an
intravenously administered anticancer agent.
The protein corona has a dual effect; it can be employed for targeting delivery,
but at the same time it can encourage the phagocytosis and rapid clearance of
nanoparticle from blood circulation. Therefore, more detailed studies are still
required to engineer protein coronas with optimum properties.
™
3.4 Toxicity
The development of in vitro protocols to assess the potential toxicity of the
nanoparticles represents a challenge because of the rapid changes of their intrinsic
physicochemical properties upon dispersion in biological fluids. Dynamic forma-
tion of protein coating around nanoparticles is a key parameter, which may strongly
impact the biological response in nanotoxicological tests. Studies of the interactions
of proteins with NPs may help understand potential biological toxicity such as
changes in protein fibrillation, exposure of new antigenic epitopes, or loss of
function such as enzymatic activity. The interface of protein corona solution is
the first primary surface which is in contact with the cells. Better understanding of
the detailed structure of this interface is the goal of nanotoxicology literatures [
4
].
