5-Aminolevulinic Acid-Mediated Photodynamic Therapy on Wound Healing: A Systemic Review of Human Evidences

Abstract

Backgrounds: Skin wounds are a kind of refractory disease frequently encountered in clinic, which brings enormous burden to patients. Great efforts to address the dilemma of wound healing have yielded some encouraging results, but they are still unsatisfactory. 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) has been developed as a promising noninvasive treatment for skin wounds. A systematic review was performed to determine the existing evidence base for the clinical use of ALA-PDT on refractory wounds. Methods: We conducted a PubMed search for English literature related to the clinical treatment of human skin ulcers by ALA-PDT published from 2012 to 2022, and performed a systematic review. Results: 25 studies were ultimately selected in the present review and summarized, including six studies of skin cancer, five studies of chronic leg ulcers, three studies of erosive pustular skin diseases, and two studies of erosive oral lichen planus symptoms. A total of 335 patients had approximately 355 ulcers, of which 315 ulcers received photodynamic therapy and 276 improved with ALA-PDT. 20% ALA solution, wavelength between 600 nm and 670 nm, energy density of 120 J/cm2, frequency of once per week and 3 sessions were the most selected therapeutic parameters. Generally, ALA-PDT for wounds was effective with main adverse events of mild to moderate pain, and follow-up was generally conducted within 1 year. Conclusions: This systematic review summarized the commonly used therapeutic parameters for ALA-PDT in the clinical treatment of skin wounds. After ALA-PDT alone or ALA-PDT combined with curettage, antibacterial and surgical treatment, all wounds healed well, and the adverse reactions were mainly mild to moderate pain, which could be relieved by cooling. ALA-PDT had proven to be a promising wound treatment modality through evidence of safety and efficacy.

Pharmacotherapy for Keloids and Hypertrophic Scars

“…Photosensitizer Prodrug (5-Aminolevulinic Acid, Methyl Aminolevulinate) Photodynamic therapy (PDT), a therapeutically promising method that involves the combined action of photosensitizers, oxygen, and light, has emerged as a therapeutically promising method for treating a broad variety of solid tumors and infectious diseases. In treating skin scars, PDT stimulates wound healing by enhancing re-epithelialization and promoting angiogenesis, as well as modulating skin homeostasis [235]. In a recent review article, it was reported that PDT using 5-aminolevulinic acid (5-ALA) as a photosensitizer has been developed as a promising noninvasive treatment for skin wounds such as skin cancer, chronic leg ulcers, and erosive pustular skin diseases, in which 20% 5-ALA solution, a wavelength between 600 nm and 670 nm (red light), an energy density of 120 J/cm 2 , a frequency of once per week and three sessions were the most widely selected therapeutic parameters [236].…”

“…When PpIX is activated by visible red light, cytotoxic ROS and free radicals are generated. This phototoxic effect can cause malignant and non-malignant hyperproliferative tissue to be destroyed, decrease in size, and eventually disappear [235,237]. In addition, topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization, promoting angiogenesis, as well as modulating skin homeostasis [238].…”