In vitro and in vivo studies employing the ALA dendron, tris methyl ALA aminomethane TFA salt

DI VENOSA G, CASAS A, BATTAH S, DOBBIN P, FUKUDA H, MACROBERT A, BATLLE A

Londres, Inglaterra

Congreso; BMLA Autumn Meeting London; 2004

British Medical Laser Association

5-aminolevulinic acid (ALA is the first intermediate in haem byosynthesis and a precursor of protoporphyrin IX (PpIX). PpIX is used as an endogenous photosensitiser in photodynamic therapy (PDT). The hydrophilic nature of the ALA molecule appears to limit its penetration through the stratum corneum of the skin. The use of hyperbranched polymers (or dendrons) is a promising alternative to deliver several ALA molecules into the cell. We synthesized a novel ALA dendron, aminomethane tris methyl ALA TFA salt (3m-ALA), bearing 3 ALA residues. We employed the LM3 mammary adenocarcinoma cell line either in vitro or subcutaneosly implanted into mice. In vitro we found that 3m-ALA is taken up by the cells with similar efficency compared toALA. We demostrate using ionic interchange extraction that 30% of the 3m-ALA was converted to ALA inside the cell. When applied topically to mice, porphyrins from 3m-ALA peaked in tumour between 4h and 7h after application. Skin overlaying the tumor accumulation was lower from 3m-ALA. These results demostrate that ALA dendrons can be hydrolyzed to release ALA and induce porphyrin biosynthesis.