TMFI Enhances Skin Surface and Epidermal PpIX Fluorescence

Normal Skin

protoporphyrin ix, 5-aminolevulinic acid, thermo-mechanical intervention, normal skin

This study investigates a relatively new device TMFI and incubation of ALA in a cream-vehicle and a gel-vehicle.

Topical photodynamic therapy (PDT) is a well-established treatment for dermatological pre-malignant actinic keratoses and Morbus Bowen as well as selected cases of basal cell carcinomas. PDT is exceedingly well suited for treatment of larger skin areas and provide excellent cosmetic results. PDT is based on the photosensitizing drug 5-aminolevulinic acid (5-ALA) that is metabolized into the light-sensitive Protoporphyrin IX, and activated in the skin by light in the visible spectrum. When skin incubated with 5-ALA subsequently is exposed to light, photoactivated PpIX catalyzes a photochemical reaction, which leads to cell apoptosis of the dysplastic or neoplastic tissue. The amount of PpIX fluorescence in the skin is estimated by PpIX fluorescence measurements on skin surface by fluorescence photographs and in the skin depth with fluorescence microscopy. Previous studies have suggested an association of the amount of PpIX in the skin and the clinical outcome of PDT. The highly lipophilic nature of the stratum corneum (SC) provides the main barrier for influx of drugs and environmental chemicals into the body (6). SC is the greatest impediment for uptake of 5-ALA and the formation of PpIX can be increased by modifying the SC. Pretreatment of the skin facilitates local uptake of photosensitizing agents and is therefore recommended to obtain optimal outcomes in PDT. Recently, different energy-based devices have been introduced for PDT pretreatment to disrupt the SC barrier and effectively increase PpIX accumulation. However, current light-based treatments, such as ablative and non-ablative lasers, are painful to patients and induce thermal damage that result in oozing, crusting or peeling of the skin. To increase cutaneous absorption with minimal damage to the skin, thermo-mechanical fractional intervention (TMFI) has been introduced as a new technology. TMFI rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates the epidermis and superficial dermis and create micropores with no coagulative damage of surrounding tissue. The amount of thermal energy delivered can be adjusted by pulse duration and by the protrusion depth of the tip that sets the thermal matching between the tip and the skin. TMFI has in one study shown to increase uptake of hydrophilic drugs compared with no skin pretreatment. As TMI dehydrates the epidermis, hydrophilic drugs dissolved in a low viscosity liquid-based vehicle may be more readily distributed within the skin compared to drugs dissolved in a high viscosity vehicle. The investigators hypothesize that i) TMFI increases 5-ALA induced PpIX accumulation compared with no pretreatment and that ii) TMFI + 5-ALA in a low viscosity vehicle formulation enhances PpIX skin biodistribution compared with 5-ALA in a high viscosity vehicle formulation. Potentially, TMFI pretreatment could improve PpIX biodistribution and reduce photosensitizer incubation time to obtain sufficient PpIX accumulation. This could significantly benefit thousands of patients who each year undergo PDT for dysplastic skin lesions.

No related papers found yet.

Denmark