The use of light-activated antimicrobial agents for the treatment of periodontitis, caries and other infectious diseases
Submitting InstitutionUniversity College London
Unit of AssessmentAllied Health Professions, Dentistry, Nursing and Pharmacy
Summary Impact TypeTechnological
Research Subject Area(s)
Medical and Health Sciences: Dentistry, Medical Microbiology
Summary of the impact
Periodontitis is a significant public health concern affecting more than
half of those over 30 years of age. Our research on light-activated
antimicrobial agents (LAAAs) has resulted in the development of a novel,
non-invasive therapy that quickly and safely treats periodontitis, thereby
reducing antibiotic usage. This technology was developed for commercial
use through a licence agreement with Ondine Biomedical and their
subsidiary company PDT Inc., as a system called Periowave. Periowave is
available in Canada, Mexico and South East Asia, has been granted CE
marking and FDA approval is currently being sought. To date an estimated
92,000 treatment kits have been sold and 313,000 patients treated. The
system has now also been adapted for use in hospitals to eradicate MRSA
from the anterior nares thereby preventing post-surgical infections.
Since 1993, a research programme on the use of light-activated
antimicrobial agents (LAAAs) to treat periodontitis, caries and other
infectious diseases has been undertaken at the UCL Eastman Dental
Institute (EDI), led by Professor Michael Wilson. LAAAs are drugs that
have no antimicrobial activity in the dark but are activated by light of
an appropriate wavelength — they are intended to supplement or replace the
use of traditional antibiotics and antiseptics and have the advantage that
microbes are very unlikely to become resistant to them as the active
moieties are singlet oxygen and free radicals. Furthermore, unlike
antibiotics, LAAAs can also inactivate a wide range of bacterial virulence
factors e.g. enzymes and lipopolysaccharides.
Initial work in 1995 focused on the potential of the technology to
prevent and/or treat oral infections. A variety of potential LAAAs were
screened for their ability to kill the wide range of bacteria involved in
the aetiology of caries, gingivitis and periodontitis. Potential LAAAs
included phenothiaziniums, cyanines, porphyrins, chlorins and
phthalocyanines — each of these had to be matched with a laser emitting
light with a wavelength corresponding to the absorbance maximum of the
LAAA. Target organisms included Streptococcus mutans,
lactobacilli, Porphyromonas gingivalis and Prevotella
intermedia. The most promising compounds were then investigated for
their effectiveness at killing the target organisms under environmental
conditions similar to those that exist in the oral cavity. Hence, the
organisms were grown as biofilms (which resemble dental plaques) and the
effects of the presence of saliva and gingival crevicular fluid on the
effectiveness of the LAAAs was studied. Optimum parameters (LAAA
concentration, light dose, light energy density) needed for killing under
these conditions were established [1, 2].
Following licensing of our patent to Ondine Biopharma in 1998, EDI
embarked on a collaborative research programme with the company to develop
a technology specifically aimed at treating periodontitis — this was named
"Periowave". Methylene blue was chosen as the LAAA because of its
antimicrobial effectiveness and safety profile and this required a laser
emitting light with a wavelength of 670 nm. Extensive studies were carried
out to determine the optimal and clinically acceptable parameters
(concentration of methylene blue, light dose, light energy density)
required to kill a range of periodontitis-associated organisms grown as
biofilms in the presence of gingival crevicular fluid. Studies involving
tissue culture and animals were also carried out to ascertain if the
optimal parameters for achieving a bactericidal effect would induce damage
to mammalian tissues. We also demonstrated that LAAAs, unlike antibiotics,
can inactivate bacterial virulence factors and can down-regulate
inflammatory processes. This ground-breaking finding means that LAAAs have
a major advantage over antibiotics in the treatment of infectious diseases
Ondine Biopharma used these findings to develop an appropriate
LAAA-containing formulation and to design a hand-held light delivery
system suitable for use by dentists. Laboratory and studies were
undertaken at EDI to confirm the effectiveness of the device for clinical
application, and this has been confirmed in further trials in the US,
Canada and China . Work is now underway to extend the use of
LAAAs in other clinical areas, for example for use in hospitals to reduce
the environmental load of pathogens thereby helping to prevent
hospital-acquired infections .
References to the research
 Bhatti M, MacRobert A, Meghji S, Henderson B, Wilson M. Effect of
dosimetric and physiological factors on the lethal photosensitization of
Porphyromonas gingivalis in vitro. Photochem Photobiol. 1997
 Efficacy of a novel light-activated antimicrobial coating for
disinfecting hospital surfaces. Ismail S, Perni S, Pratten J, Parkin I,
Wilson M. Infect Control Hosp Epidemiol 2010; 32: 1130-1132. http://dx.doi.org/10.1086/662377
Evaluation of photodynamic therapy for the treatment of biofilm-related
infections. Ondine Biopharma. 2000-5. £300,000
Light-activated antimicrobials in the prevention/treatment of
methicillin-resistant Staphylococcus aureus infections (with Nair
S and Cookson B). Medical Research Council. 2001-4. £152,904
Control of microbial contamination of surfaces in hospitals using
light-activated antimicrobial agents. Charles Wolfson Charitable Trust.
Improving the delivery of 5-aminolaevulinic acid in photodynamic therapy:
synthesis and biological studies of novel peptide prodrugs (with I.
Eggleston and A. MacRobert). BBSRC. 2006-9. £440,097
Light-activated antimicrobial agents. (with S. Nair, I. Parkin, Q.
Pankhurst, M. Singer). Ondine Biopharma Inc. 2005-8. £456,000
Chemical vapour deposition for the generation of visible light-activated
antimicrobial coatings (with Ivan Parkin, Jon Pratten). EPSRC. 2007-10.
Light-activated antimicrobial polymers for the prevention of
catheter-associated infections (with Ivan Parkin, Jon Pratten). BBSRC.
The use of light-activated antimicrobials to prevent catheter-related
infections. (with Parkin I, Pratten J, MacRobert AJ, Mosse S, Kay C).
Medical Research Council. 2011-3. £1,100,327
Details of the impact
Our research has resulted in a new treatment for periodontitis,
Periowave, that provides significant benefits over existing antibiotic
(and potentially invasive surgical) treatments. The technology we
developed was licensed to Ondine Biomedical in 1998 for periodontal
treatment. Over the following eight years, the company undertook a number
of collaborative projects with the EDI, including sponsoring a clinical
trial. UCL has received more than £1m in research investment from Ondine
to develop and evaluate this technology. Licensing income received by UCL
from the commercialisation of the patents is approximately £0.4m. Further
income is also anticipated as a consequence of the technology being
licensed to Ondine for the treatment of caries [a].
Through this collaboration, Ondine developed the Periowave system. This
consists of a hand-held light-emitting device and a syringe containing the
LAAA. A solution of the LAAA is applied to the disease site by a dentist,
who then irradiates it with light from the athermal laser for 60 seconds.
The treatment takes only a few minutes overall and is painless and
stress-free, compared to a long course of antibiotics (up to seven days)
or repeated scaling of teeth. This reduces concerns of limited patient
compliance and the risk of adverse side effects of antibiotics and/or
conventional periodontal treatment [b].
Periowave has been available commercially in Canada since 2006, and has
since been licensed in Japan, Hong Kong, Singapore and Mexico. The system
is currently under review by the Korea Food & Drug Administration. It
has also been given CE marking by the EC. Six core staff are employed by
Periowave Dental Technologies in sales and marketing, along with a network
of distributors in various countries. To date approximately 92,000
Periowave treatment kits have been bought and used on an estimated 313,000
patients. Aside from trial data indicating clinical benefit, clinicians
and patients have attested to its benefits. Comments include:
"Periowave photodisinfection is a rapid, painless approach to removal
of the harmful bacteria."
"Periowave is a painless and stress- free way to control the health of
"My first Periowave treatment was just great. It was completely
painless, and it was interesting to hear scientifically what was going
on. There was absolutely no discomfort. If somebody gave me a choice
between Periowave and an antibiotic, I would take Periowave™ in a flash.
No antibiotics!" [c].
The principles of LAAAs and Periowave have wider impacts on public health
than periodontitis. One of the main problems confronting medicine in the
21st century is the increasing prevalence of
antibiotic-resistant bacteria. This, combined with a shortage of new
antibiotics under development, means that the ability to treat infectious
diseases is diminishing. A further impact of our work on LAAAs has thus
been their adaption for the prevention and/or treatment of other
infections. Based directly upon the principles of Periowave (see company
website [d]) Ondine have now developed a system (MRSAidTM)
for eradication of methicillin-resistant Staphylococcus aureus
from the nose [e]. A recent study conducted by Vancouver General
Hospital of 5,000 patients revealed that use of this nasal
photodisinfection system reduced post-surgical infection by almost 40 per
cent and saved the hospital $1.3m in costs relating to post-surgical
infections and re-admissions. The hospital was awarded a prize for
innovation by the International Consortium for Prevention and Infection
Control (ICPIC) in Geneva for this work, and have now adopted the system
into routine clinical practice [f].
Further applications of the principles of LAAAs are presently being
investigated for: (i) preventing catheter-associated infections (by
fabricating catheters from LAAA-containing polymers), (ii) reducing the
microbial load on hospital surfaces (by coating surfaces with
LAAA-containing polymers) and (iii) preventing wound infections (using
dressings containing LAAAs).
Sources to corroborate the impact
[a] Details of licensing and commercial benefits to Ondine (including
sales data provided by the company) can be verified by UCL Business.
Contact details provided.