ALA and ALA hexyl ester in free and liposomal formulations for the photosensitisation of tumour organ cultures

• Published in: British journal of cancer 2002-03, Vol.86 (5), p.837-842
• Main Authors: Casas, A, Perotti, C, Saccoliti, M, Sacca, P, Fukuda, H, del C Batlle, A M
• Format: Article
• Language: English
• Subjects: Acids; Aminolevulinic Acid - administration & dosage; Aminolevulinic Acid - analogs & derivatives; Aminolevulinic Acid - pharmacokinetics; Aminolevulinic Acid - pharmacology; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Experimental Therapeutics; Liposomes; Male; Medical research; Medical sciences; Mice; Mice, Inbred BALB C; Microscopy; Microscopy, Electron; Mitochondria; Molecular Medicine; Oncology; Photochemotherapy; Photodynamic therapy; Photoradiation therapy and photosensitizing agent; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Porphyrins - biosynthesis; Porphyrins - pharmacokinetics; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600144

In spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed at improving 5-aminolevulinic acid transmembrane access. In this study we used both 5-aminolevulinic acid and its hexyl ester in their free and encapsulated formulations to compare their corresponding endogenous synthesis of porphyrins. Employing murine tumour cultures, we found that neither the use of hexyl ester nor the entrappment of either 5-aminolevulinic acid or hexyl ester into liposomes increase the rate of tumour porphyrin synthesis. By light and electronic microscopy it was demonstrated that exposure of tumour explants to either free or liposomal 5-aminolevulinic acid and subsequent illumination induces the same type of subcellullar damage. Mitochondria, endoplasmic reticulum and plasma membrane are the structures mostly injured in the early steps of photodynamic treatment. In a later stage, cytoplasmic and nuclear disintegration are observed. By electronic microscopy the involvement of the endocytic pathway in the incorporation of liposomal 5-aminolevulinic acid into the cells was shown.