Skin Laser Treatments Enhancing Transdermal Delivery of ALA
Section snippets
INTRODUCTION
Photodynamic therapy (PDT) involves a combination of a photosensitizer, light, and oxygen to cause destruction of selected cells, mainly through generation of highly cytotoxic singlet oxygen.1 Common photosensitizers, such as porphyrins, cannot be administered by topical application to neoplastic skin lesions, because their high molecular weights preclude successful penetration of the stratum corneum (SC). When administered intravenously, these agents accumulate in normal skin and lead to
Chemicals
ALA (5-aminolevulinic acid, hydrochloride salt) was obtained from Sigma–Aldrich, Madrid, Spain. Trypsin (trypsin from bovine pancreas 13,000 U/mg) was obtained from Sigma–Aldrich. All other chemicals were of analytical reagent grade.
Skin Samples
Pinna skin of the inner side of rabbit ear (New Zealand rabbits of 2.9–3.1 kg from Granja Conicular San Bernardo, Navarra, Spain) was used for skin permeation studies. The animals were sacrificed and the ears were removed. Pinna skin was peeled away from the
RESULTS
In order to assess the effect of the radiation from both Er:YAG laser and second harmonic of Nd:YAG laser on the integrity of the skin structure, pinna skin of the inner side of rabbit ear was irradiated, with laser fluences in the range of 1–1.6 J/cm2 at 2940 nm and 6.6–7 J/cm2 at 532 nm. Higher repetition rates were needed at 532 nm (15 Hz) than at 2940 nm (1–2 Hz) in order to achieve an increase in the drug permeability.
The cumulative amount of ALA (mg/cm2) in the receptor compartment as a function
DISCUSSION
The increased porphyrin accumulation in tumors as compared to normal skin associated with topical ALA occurs because ALA, being a water-soluble molecule, penetrates normal SC poorly. Neoplastic skin lesions are thought to possess a compromised SC barrier that allows enhanced ALA penetration. Maximum tumor-to-normal tissue ratios are observed 3–6 h after topical administration and can be as high as 18:1.18 However, prolonged application times cause widespread skin fluorescence and ALA and PpIX
CONCLUSIONS
In this study we show that the laser treatment was capable of delivering sufficient ALA through the skin by SC ablation. Er:YAG and second harmonic of Nd:YAG laser radiations can modulate skin histology and transdermal drug delivery, although the particular characteristics of the laser radiation–skin interaction depend on the their own parameters of actuation, mainly wavelength and pulse duration. SC laser removal requires the appropriate selection of fluences and repetition rates in order to
ACKNOWLEDGEMENTS
The work described in the present study was supported by Intramural Project 200880I215 of the Spanish CSIC. In addition the authors wish to thank Dr. Roberto Sastre and Dr. Olga García for their assistance in Differential Scanning Calorimetry.
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