CONICET | Buscador de Institutos y Recursos Humanos

: Photodynamic Therapy (PDT) is a non-thermal technique for inducing tissue damage with light following administration of a light-activated photosensitising drug which can be selectively retained in malignant or diseased lesions relative to normal adjacent tissue. The use of endogenous Protoporphyrin generated through the heme biosynthetic pathway after administration of 5-aminolevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). We designed liposomes of different compositions to improve delivery of ALA and its esterified derivatives ALA-Hexyl ester (He-ALA) and ALA-Undecanoyl ester (Und-ALA) for its use in Photodynamic Therapy (PDT). We employed egg yolk phosphatidyl choline (PC), egg lecithin phosphatidic acid (PA) and egg yolk lecithin phosphatidyl glycerol (PG) in the composition of the liposomes. We prepared small unilamellar vesicles of PC, PC:PG (80:20) or PC:PA (80:20) containing ALA or derivatives and purified by a minicolumn centrifugation method. Liposomes of 100% PC resulted in percentages of entrapment of around 6% for 2 mM ALA, 13% for 2mM He-ALA and 51% for 2 mM Und-ALA.Addition of PC or PG to the formulation, resulted in increased rates of entrapment: 19% for 2mM ALA, 69% for 2 mM He-ALA and 87% for 2 mM Und-ALA in PC:PG (80:20) and21% for 2mM ALA, 60% for 2 mM He-ALA and 86% for 2 mM Und-ALA in PC:PA (80:20).Higher concentrations of ALA or derivatives resulted in lower percentages of entrapment. The three formulations containing ALA or derivatives were stable up to 1 week upon storage at 4°C. Incubation of empty liposomes of the three compositions with ALA or its derivatives resulted in a significant entrapment, showing diffusion of the molecules into the vesicles.