ARTICLE | dermatology |
depending on the target, have adequate fluence and duration so as to induce a Pdt reaction, and have minimal side-effects25
. MAL
Intracellular enzymes
ALA O2 Red light
• Blue lasers: argon 488nm, 514nm • Broadband red light (550–700nm) • Red diode (635nm) laser-mediated PDT • Red lasers: copper vapour-dye, Nd:YAG • Long-pulsed pulsed dye laser-PDT
the light source that may be used for Pdt is defined by PplX Photosensitiser
• Cytotoxic oxygen species • Cellular damage • Cellular death • Destruction of Propionibacterium acnes • Decrease of the size of the sebaceous gland • Decrease seborrhea
delivery of a photosensitiser followed by irradiation
with visible light, at doses that are not harmful. When irradiated, the sensitiser activates molecular oxygen to generate reactive oxygen species (roS), such as singlet oxygen (o2
), hydrogen peroxide (H2 o2 ), and free radicals
such as the hydroxyl radical (-oH) and the superoxide anion (o2
-), which have a cytotoxic effect and cause
nucleic acid oxidation, mitochondrial disruption, and lipid peroxidation. these mechanisms manifest as cellular apoptosis, necrosis, vascular compromise, and immunologic changes 13, 21
. topical ala is not a photosensitiser alone, but is taken
up by epithelial cells and metabolised to photosensitive protoporphyrin IX (PpIX), a precursor of haem, through the porphyrin metabolic pathway. PpIX is then activated by the delivery of visible light, and it reacts with oxygen to produce oxygen species and monobaric oxygen, resulting in membrane damage and cell destruction11
.
Permanent bleaching of the porphyrin by the singlet oxygen produced during Pdt is called photobleaching22
.
PpIX is cleared by the body within 24–48 hours, minimising the period of photosensitisation23
. the supposed mechanisms of action for optical
treatments in acne include photothermal heating of sebaceous glands, and photochemical inactivation of P. acnes, which produces coproporphyrins and protoporphyrins. Furthermore, a photoimmunological reaction may contribute to acne improvement4
.
Pdt may also promote improvements in acne via antibacterial activity against P. acnes, selective damage to sebaceous glands, reduction in follicular obstruction by keratinocyte shedding and via immunologic changes11, 17, 24
(Figure 1).
Lights sources used in PDT the ideal light source for topical Pdt should be optimally absorbed by the photosensitiser, penetrate adequately
46 ❚ July 2011 |
prime-journal.com
Figure 1 Mode of action of photodynamic therapy in acne (ALA= aminolaevulinic acid; MAL= methyl aminolaevulinic acid; PDT=photodynamic therapy; PpIX= photosensitive protoporphyrin IX)
the absorption spectrum of the photosensitiser, light wave length, and light penetrance depth. light sources that have been used in Pdt include filtered xenon-arc and metal–halide lamps, fluorescent lamps, light-emitting diodes (leds), and lasers. Non-laser light sources are popular in topical Pdt, possessing the advantages over lasers of being inexpensive, stable, easy to operate, requiring little maintenance, and providing wide-area illumination fields. led sources include the aktilite 16 and 128 (galderma) and the omnilux (Photo therapeutics ltd, altrincham, UK). these led sources match the 630/635 nm activation peak of PpIX, while excluding the extraneous wavelengths present in broadband sources, thus allowing for shorter irradiation times5
. PpIX has its largest absorption peak in the blue region
at 410 nm (Soret band: 360–400 nm), with four smaller absorption peaks at 505, 540, 580 and 630 nm. UVa and blue light lie within the Soret band. However, UV treatment (UVa, UVB) has shown limited therapeutic effect in acne, and its use is not justified for this condition given the risk of photocarcinogenesis and the need for repeated treatment sessions26
. the penetrance depth is increased analogously to the
wavelength in the visible spectrum. a 50% penetrance corresponds to 80 μm for 355 nm lasers, and increases to 1200 μm for 694 nm lasers. the shorter wavelengths penetrate no further than 90–150 μm (the superficial vascular plexus) because melanin readily absorbs them and they are scattered within the dermis. this is hardly enough to have a significant effect on the bulk of the sebaceous glands, which lie at an approximate depth of 1.3 mm13
. However, ashkenazi et al demonstrated The ideal
light source for topical PDT should be optimally absorbed by the photosensitiser, penetrate adequately depending on the target, have adequate fluence and duration so as to induce a PDT reaction, and have minimal side-effects.
that through endogenous porphyrin production, particularly coproporphyrin III, P. acnes can be temporarily eradicated via a photodynamic reaction with blue light irradiation27
. most light sources for Pdt
aim to use the 630 nm absorption peak in the red region in order to improve tissue penetration5
. the penetration
depths for wavelengths within the yellow–red range fall between 230 and 750 μm. Wavelengths within the infrared and radio frequence ranges should penetrate even further, but wavelengths above 850 μm do not have sufficient energy to produce singlet oxygen23
. therefore,
a balance between depths of penetration and the quantum yield of oxygen is required when choosing the light source13
. red light is less effective than blue light for activation
of porphyrins, but penetrates deeper in the skin. It also has anti-inflammatory properties, playing a role in the production of cytokines from macrophages or other cell types. these cytokines stimulate fibroblast proliferation and the production of growth factors, therefore contributing to inflammation26
. Blue light phototherapy
resulted in significant improvement in both inflammatory and non-inflammatory acne lesions, without a decrease in P. acnes colony counts28
. another study showed that
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