Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin

Photodynamic therapy (PDT) is a popular technique for skin cancer treatment. Protoporphyrin IX, which is a photosensitizing agent, converted enzymatically from the prodrug 5-aminolevulinic acid (ALA), is used as a photosensitizer in PDT for cancer. However, ALA penetrates with difficulty through intact skin; therefore, improving delivery systems for ALA in the skin will play an important role in ALA-PDT. Enhancement of ALA skin penetration can be achieved by physical methods, such as iontophoresis, laser, microneedles, ultrasound, and by adding chemical penetration enhancers, such as, dimethyl sulfoxide, oleic acid, and others, whereas some researches used lipophilic ALA derivatives and different vehicles to improve the transdermal delivery of ALA. This review introduces several enhancement techniques for increasing ALA permeation through the skin.