Biomedical Engineering Reference
In-Depth Information
these materials and biological systems
[25]
. The interface comprises three interacting components:
(i) the surface of the nanoparticle, (ii) the solid
liquid interface and the effects of the surrounding
medium, and (iii) the contact zone with biological substrates. The nanoparticle characteristics of
most importance as regards interaction with biological systems, whether mammalian or microbial,
are chemical composition, surface function, shape and number of sides, porosity and surface crys-
tallinity, heterogeneity, roughness, and hydrophobicity or hydrophilicity
[102]
. For example, it has
been shown that titanium dioxide nanoparticles
[103]
act to resist the formation of surface biofilms
through increased hydrophilicity in comparison to an unmodified surface.
The characteristics of the surface layer, such as zeta charge, nanoparticle aggregation, dispersion
state, stability, and hydration as influenced by the characteristics of the surrounding medium
(including ionic strength, pH, temperature, and presence of organic molecules or detergents) are
critically important. The contribution of surface charge to both mammalian and microbial interac-
tions has been illustrated using surfactant-coated nanoparticles
[104]
. Antiadherent and antifungal
effects were shown using buccal epithelial cells treated with nondrug-loaded poly(ethylcyanoacry-
late) nanoparticles. Nanoparticles were prepared using emulsion polymerization and stabilized with
cationic, anionic, or nonionic surfactants. Cationic surfactants, for example, cetrimide, which are
known antimicrobial agents, were the most effective in reducing C. albicans blastospore adhesion,
and showed a growth inhibitory and biocidal effect against the yeast. Production of nanoparticles
with an anionic surfactant gave lower yields and wide particle-size distributions. No evidence of
killing against C. albicans was shown. Nonionic surfactant-coated nanoparticles produced interme-
diate kill rates. These studies clearly demonstrate the importance of surface charge on the
nanoparticle surface. It is suggested that the buccal epithelium could possibly be treated using
polymeric-type nanoparticles in a mouthwash-type formulation; in theory, this would prime the
potential target cells against adhesion and infection.
The in vivo screening of around 130 nanoparticles intended for therapeutic use has allowed
detailed assessments as regards biocompatibility
[25]
. It was shown that the main independent par-
ticle variables which determine compatibility are size, surface charge, and dispersibility (particu-
larly the effect of hydrophobicity). Cationic particles or particles with a high surface reactivity are
more likely to be toxic (to both eukaryotes and prokaryotes). Larger, more hydrophobic or poorly
dispersed particles, which would be rapidly removed by the reticuloendothelial system, were shown
to be less toxic. Karlsson et al.
[60]
have shown that metal oxide nanoparticles are more toxic than
at first envisaged at concentrations down to 40
g/mL and show a high variation as regards differ-
ent nanoparticle species to cause cytotoxicity, DNA damage, and oxidative DNA lesions. Toxic
effects on cultured cells were assessed using trypan blue staining, the comet assay to measure DNA
damage and an oxidation-sensitive fluoroprobe to quantify the production of ROS
[60]
. Copper
oxide was found to be the most toxic and therefore may pose the greatest health risk.
Nanoparticulate ZnO and TiO
2
, both ingredients in sunscreens and cosmetics, also showed signifi-
cant cytotoxic and DNA-damaging effects. The potential mechanisms of toxicity for these and other
selected nanoparticles are listed in
Table 10.1
.
In order to help prevent aggregation of nanoparticles, stabilizing (capping) agents that bind to
the entire nanoparticle surface can be used; these include water-soluble polymers, oligo- and poly-
saccharides, sodium dodecyl sulfate, polyethylene glycol, and glycolipids. The specific impact of
surface capping, size scale, and aspect ratio of ZnO particles upon antimicrobial activity and cyto-
toxicity have been investigated
[105]
. Polyethylene glycol-capped ZnO nanoparticles demonstrated
μ
