Current Advances in 5-Aminolevulinic Acid Mediated Photodynamic Therapy

Abstract

Kennedy and Pottier discovered that photodynamic therapy (PDT) could be carried out using a procedure consisting of topical application of the porphyrin-precursor, 5-aminolevulinic acid (ALA) to the skin, followed after some time by illumination with various light parameters in the 1980s. Since then, ALA-PDT has expanded enormously and now covers most aspects of dermatological disease. The purpose of this review is to discuss a range of ingenious strategies that investigators have devised for improving the overall outcome (higher efficiency and lower side effects) of ALA-PDT. The big advance of using ALA esters instead of the free acid to improve skin penetration was conceived in the 1990s. A variety of more recent innovative approaches can be divided into three broad groups: (a) those relying on improving delivery or penetration of ALA into the skin; (b) those relying on ways to increase the synthesis of protoporphyrin IX inside the skin; (c) those relying on modification of the illumination parameters. In the first group, we have improved delivery of ALA with penetration-enhancing chemicals, iontophoresis, intracutaneous injection, or fractionated laser. There is also a large group of nanotechnology-related approaches with ALA being delivered using liposomes/ethosomes, ALA dendrimers, niosomes, mesoporous silica nanoparticles, conjugated gold nanoparticles, polymer nanoparticles, fullerene nanoparticles, and carbon nanotubes. In the second group, we can find the use of cellular differentiating agents, the use of iron chelators, and the effect of increasing the temperature. In the third group, we find methods designed to reduce pain as well as improve efficiency including fractionated light, daylight PDT, and wearable light sources for ambulatory PDT. This active area of research is expected to continue to provide a range of intriguing possibilities.

Photodynamic therapy in dermatology beyond non-melanoma cancer: An update

“…However when exogenous ALA (or the easily hydrolyzed methyl ester of ALA called MAL) is added to the system, PPIX accumulates in the cels since the final enzyme (ferrochelatase) is then rate-limiting (Fig. 2) [6]. The accumulated excess of PPIX generates ROS after illumination leading to apoptosis and necrosis of targeted tissue.…”

5-aminolevulinic acid (5-ALA) fluorescence-guided Mohs surgery resection of penile-scrotal extramammary Paget's disease

“…Photodynamic diagnosis has been utilized intraoperatively to detect positive surgical margins (21). Over the last decade, 5-aminolevulinic acid (5-ALA) has acquired considerable attention as a feasible agent for photodynamic diagnosis and therapy.…”

“…Increasing the incidence of complete resection, without causing excess morbidity, requires new methods to accurately identify neoplastic tissue intraoperatively, such as use of the drug 5-aminolevulinic acid (5-ALA). It is utilized as a precursor of a photosensitizer for performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) to confirm and kill tumor cells (6)(7)(8). In …”

Shedding light on photodynamic therapy for basal cell carcinoma

“…In those studies, intravenous porphyrin derivatives and visible light were used. Topical PDT treatment, currently widely performed in dermatology, uses topically applied 5‐aminolaevulinic acid (ALA) or ALA esters . ALA is converted to protoporphyrin IX in the epidermis.…”