Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and hexyl 5-aminolaevulinate on normal human skin

Juzeniene, Asta; Juzenas, Petras; W., L.; Iani, Vladimir; Moan, Johan Emelian

doi:10.1111/j.1365-2133.2006.07484.x

Cited by 60 publications

(56 citation statements)

References 65 publications

(133 reference statements)

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“…ALA and MAL produce the same intracellular photosensitizer (PpIX), penetrate human skin to similar depths and produce a similar spatial distribution of PpIX in murine skin . However, ALA produces relatively greater amounts of PpIX (Juzeniene et al, 2006) and higher levels of fluorescence with a slower time course than MAL in human skin (Lesar et al, 2009). This, together with greater local edema reported after ALA compared with MAL-PDT in mice and the possibility of different microscopic PpIX distributions following ALA and MAL application to human skin, could explain the greater immunosuppression observed after ALA-PDT in our study.…”

Section: Discussioncontrasting

confidence: 53%

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Frost

Halliday

Damian

2011

Journal of Investigative Dermatology

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Photodynamic therapy (PDT) of non-melanoma skin cancers currently carries failure rates of 10-40%. The optimal irradiation protocol is as yet unclear. Previous studies showed profound immunosuppression after PDT, which may compromise immune-mediated clearance of these antigenic tumors. Slower irradiation prevents immunosuppression in mice, and may be at least as effective as high-fluence-rate PDT in preliminary clinical trials. The photosensitizers 5-aminolaevulinic acid and/or methyl aminolaevulinate were applied to discrete areas on the backs of healthy Mantoux-positive volunteers, followed by narrowband red light irradiation (632 nm) at varied doses and fluence rates. Delayed type hypersensitivity (Mantoux) reactions were elicited at test sites and control sites to determine immunosuppression. Human ex vivo skin received low- and high-fluence-rate PDT and was stained for oxidative DNA photolesions. PDT caused significant, dose-responsive immunosuppression at high (75 mW cm(-2)) but not low (15 or 45 mW cm(-2)) fluence rates. DNA photolesions, which may be a trigger for immunosuppression, were observed after high-fluence-rate PDT but not when light was delivered more slowly. This study demonstrates that the current clinical PDT protocol (75 mW cm(-2)) is highly immunosuppressive. Simply reducing the rate of irradiation, while maintaining the same light dose, prevented immunosuppression and genetic damage and may have the potential to improve skin cancer outcomes.

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Section: Discussioncontrasting

confidence: 53%

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Frost

Halliday

Damian

2011

Journal of Investigative Dermatology

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“…Follicles and sebaceous glands are localized relatively deeply in the skin. 38 Christiansen et al 2 suggested that liposome-loaded ALA is preferentially absorbed in hair follicles. The nanoemulsions developed in this work likely exerted similar effects as liposomes.…”

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confidence: 99%

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

Zhang

Al‐Suwayeh²,

Hung³

et al. 2011

IJN

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The study evaluated the potential of nanoemulsions for the topical delivery of 5-aminolevulinic acid (ALA) and methyl ALA (mALA). The drugs were incorporated in oil-in-water (O/W) and water-in-oil (W/O) formulations obtained by using soybean oil or squalene as the oil phase. The droplet size, zeta potential, and environmental polarity of the nanocarriers were assessed as physicochemical properties. The O/W and W/O emulsions showed diameters of 216–256 and 18–125 nm, which, respectively, were within the range of submicron- and nano-sized dispersions. In vitro diffusion experiments using Franz-type cells and porcine skin were performed. Nude mice were used, and skin fluorescence derived from protoporphyrin IX was documented by confocal laser scanning microscopy (CLSM). The loading of ALA or mALA into the emulsions resulted in slower release across cellulose membranes. The release rate and skin flux of topical drug application were adjusted by changing the type of nanocarrier, the soybean oil O/W systems showing the highest skin permeation. This formulation increased ALA flux via porcine skin to 180 nmol/cm 2 /h, which was 2.6-fold that of the aqueous control. The CLSM results showed that soybean oil systems promoted mALA permeation to deeper layers of the skin from ∼100 μm to ∼140 μm, which would be beneficial for treating subepidermal and subcutaneous lesions. Drug permeation from W/O systems did not surpass that from the aqueous solution. An in vivo dermal irritation test indicated that the emulsions were safe for topical administration of ALA and mALA.

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“…Because factors other than MAL concentration can affect the metabolism of MAL to porphyrins, it is unlikely that local porphyrin accumulation is strictly proportional to local MAL concentration. However it is well established that porphyrin accumulation increases with increasing concentrations of ALA and MAL [26][27][28]. Fluorescence microscopy of porphyrins is a surrogate for indirectly visualizing ALA or MAL uptake in skin.…”

Section: Introductionmentioning

confidence: 99%

Fractional CO₂ laser‐assisted drug delivery

et al. 2010

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Background and Objectives: Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO 2 laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug. Materials and Methods: Two Yorkshire swine were treated with single-hole CO 2 laser AFR and subsequent topical application of MAL (Metvix 1 , Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 mm. AFR was performed with a 10.6 mm wavelength prototype CO 2 laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse. Results: AFR created cone-shaped channels of approximately 300 mm diameter and 1,850 mm depth that were surrounded by a 70 mm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P<0.0011) and dermis (P<0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 mm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 mm from the holes (1,000, 1,800 mm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR. Conclusions: Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications. Lasers Surg.

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Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and hexyl 5-aminolaevulinate on normal human skin

Abstract: The concentrations inducing half of the maximal PpIX fluorescence are around 2% for ALA, 8% for MAL and 1% for HAL.

Cited by 60 publications

References 65 publications

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

Fractional CO₂ laser‐assisted drug delivery

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Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and hexyl 5-aminolaevulinate on normal human skin

Abstract: The concentrations inducing half of the maximal PpIX fluorescence are around 2% for ALA, 8% for MAL and 1% for HAL.

Cited by 60 publications

References 65 publications

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Oil components modulate the skin delivery of 5-aminolevulinic acid and its ester prodrug from oil-in-water and water-in-oil nanoemulsions

Fractional CO2 laser‐assisted drug delivery

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Product

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Fractional CO₂ laser‐assisted drug delivery