Biomedical Engineering Reference
In-Depth Information
CPP
[92]
. Use of this technology has demonstrated anticariogenic activity under both in vitro and
in vivo conditions. The levels of calcium and phosphate ions in supragingival plaque have been
shown to increase upon delivery of CPP
ACP in a mouth rinse form and promote remineralization
of enamel subsurface lesions
[91]
. Analysis of plaque samples demonstrated CPP
ACP nanocom-
plexes to be localized in plaque on the surface of bacterial cells and essentially confirm the studies
by Rose
[93,94]
who demonstrated tight binding to S. mutans and the intercellular plaque matrix to
provide a calcium ion reservoir. As a result of interaction with calcium binding sites and the mask-
ing of bacterial receptors on salivary molecules, CPP
ACP is thought to reduce bacterial coloniza-
tion as shown with CPP
ACP germanium treated surfaces
[90]
.
10.5
Photodynamic therapy and the use of nanoparticles
to control oral biofilms
Photodynamic therapy (PDT) is very well suited for the control of bacteria in oral plaque biofilms
where there is relatively easy access for the application of the photosensitizing agent and light
sources to areas requiring treatment
[95]
. This approach is now being utilized within the clinical set-
ting in some countries. The killing of microorganisms with light depends upon cytotoxic singlet oxy-
gen and free-radical generation by the excitation of a photoactivatable agent or sensitizer. The result
of excitation is that the sensitizer moves from an electronic ground state to a triplet state which then
interacts with microbial components to generate cytotoxic species
[96]
. One of the advantages of
light-activated killing is that the resistance to action of singlet oxygen is unlikely to become wide-
spread in comparison to that experienced with more traditional chemical antimicrobial agents.
A sensitizer ideally should absorb light at red to near-infrared wavelengths because these wavelengths
are able to penetrate more. The most commonly tested sensitizers on bacteria are tricyclic dyes (e.g.,
methylene blue and erythrosine), tetrapyrroles (e.g., porphyrins), and furocoumarins (e.g., psoralen).
The use of nanoparticles within this area is now under investigation. For example, a complex of bio-
degradable and biocompatible poly(lactic-co-glycolic acid) and colloidal gold nanoparticles, loaded
with methylene blue and exposed to red light at 665 nm, have been tested against planktonic
E. faecalis andinexperimentallyinfectedrootcanals
[97]
. In theory, gold nanoparticle conjugates
should have improved binding and cell wall penetration properties, and so should deliver a higher
concentration of photoactive molecules. It remains to be fully established whether such conjugates
will show an increased antibacterial activity when compared to more conventional treatments.
Most work on light-activated killing has been performed using suspensions of planktonic bacte-
ria, with relatively few studies observing biofilm-grown microorganisms. In vitro biofilm-grown
S. mutans cells demonstrated a 3-log reduction when treated with erythrosine and white light
(500
650 nm)
[98]
, while an approach using antibody- and erythrosine-labeled nanoparticles has
shown the potential for targeting specific bacterial species in oral plaque biofilms (S. Wood et al.,
unpublished observations). These in vitro studies, employing constant-depth film fermenters with
gold nanoparticles conjugated to erythrosine and antibody to either S. mutans or Lactobacillus
casei, have shown specific killing of target organisms in mixed biofilm cultures.
Considerations in relation to the therapeutic use of light-activated killing of biofilms on host
surfaces include (i) direct toxicity of the sensitizer, (ii) indirect toxicity of the sensitizer in terms of
