Characterisation of liposomes of aminolevulinic acid and derived esters

DI VENOSA G, CASAS A, HERMIDA L, FUKUDA H, DEFAIN MV, MACROBERT A, BATLLE A.

Rotterdam, Holanda

Congreso; Porphyrins and Porphyrias 2007; 2007

Erasmus MC University Medical Center Rotterdam

Liposomes of different compositions have been designed to improve delivery of aminolevuninic acid (ALA) and its esterified derivatives ALA-Hexyl ester (He-ALA) and ALA-Undecanoyl ester (Und-ALA) for its use in Photodynamic Therapy (PDT). Egg yolk phosphatidyl choline (PC), egg lecithin phosphatidic acid (PA) and egg yolk lecithin phosphatidyl glycerol (PG) were employed in the composition of the liposomes. Small unilamellar vesicles equal or less to 0.2 µm size of PC, PC:PG (80:20) or PC:PA (80:20) containing ALA or derivatives were prepared 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) and  21% 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.