Topical application of ALA and ALA hexyl ester on a subcutaneous murine mammary adenocarcinoma: tissue distribution.
Although 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has proven to be clinically beneficial for the treatment of certain cancers, including a variety of skin cancers, optimal tissue localisation still remains a problem. An approach to improve the bioavailability of protoporphyrin IX (PpIX) is the use of ALA derivatives instead of ALA. In this work, we employed a subcutaneous murine mammary adenocarcinoma to study the tissue distribution pattern of the ALA hexyl ester (He-ALA) in comparison with ALA after their topical application in different vehicles. He-ALA induced porphyrin synthesis in the skin overlying the tumour (SOT), but it did not reach the tumour tissue as efficiently. Only 5 h after He-ALA lotion application, tumour porphyrin levels surpassed control values. He-ALA delivered in cream induced a substantially lower porphyrin synthesis in SOT, reinforcing the importance of the vehicle in the use of topical PDT. Porphyrin levels in internal organs remained almost within control values when He-ALA was employed. The addition of DMSO to ALA formulation slightly increased tumour and SOT porphyrin biosynthesis, but it did not when added to He-ALA lotion.
Perotti
C
C
Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET and Department of Biochemistry, Facultad de Ciencas Exactas y Naturales, University of Buenos Aires, Argentina.
Casas
A
A
Fukuda
H
H
Sacca
P
P
Batlle
A
A
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D000818:Animals; D004195:Disease Models, Animal; D004952:Esters / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D017319:Photosensitizing Agents / Q000493:pharmacokinetics; D011166:Porphyrins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D004952:Esters; D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester