Enhancement of photodynamic therapy by use of aminolevulinic acid/glycolic acid drug mixture.
5-aminolevulinic acid (5-ALA) is a precursor in synthesis of endogenous porphyrins used to sensitize tumor tissues in photodynamic therapy (PDT). It is administered topically into a tumor which after the certain time, required for porphyrins to accumulate, is irradiated with visible light from the proper source at established wavelength. Our main aim in the present study was to increase the penetration of 5-ALA through the skin and other tissues by addition of glycolic acid (GA) to 5-ALA on cell lines in vitro and on animals. We also applied 5-ALA ointment with glycolic acid to patients suffering from squamous cell carcinoma (SCC). In our study, we used 5-ALA, dimethyl sulfoxide (DMSO), ethylenediaminetetraacetic acid, disodium salt (EDTA) and GA together in one formulation (5-ALA-GA) on eucerin support. We compared both therapeutic and cosmetic effects in 5-ALA-GA-PDT and in control group of patients. Our results showed that modification of 5-ALA ointment by addition of 5% GA caused that the treated lesions responded with rapid regression. In 12 patients with single lesions of SCC type subjected to 5-ALA-GA-PDT, we observed 100% regression of tumors following single or repeated two-three times PDT. In vitro and in vivo in animals total porphyrin levels after addition of 5% GA increased significantly (P<0.01). These results provide evidence that addition of glycolic acid should be considered as the agent which enhances 5-ALA penetration in tissues and thus increases the effectiveness of photodynamic therapy.
Ziolkowski
Piotr
P
Department of Pathology, Wroclaw Medical University, 50368 Wroclaw, Poland. ziolkows@anpat.am.wroc.pl
Osiecka
Beata J
BJ
Oremek
Gerhard
G
Siewinski
Maciej
M
Symonowicz
Krzysztof
K
Saleh
Yousif
Y
Bronowicz
Andrzej
A
D000230:Adenocarcinoma / Q000188:drug therapy; D000279:Administration, Cutaneous; D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage; D004492:Edetic Acid / Q000008:administration & dosage; D005260:Female; D005347:Fibroblasts; D006016:Glycolates / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
D006016:Glycolates; D017319:Photosensitizing Agents; C031149:glycolic acid; D000622:Aminolevulinic Acid; D004492:Edetic Acid; D004121:Dimethyl Sulfoxide