Vesicle-forming properties of new phospholipid analogues derived from N-phosphonoacetyl-L-aspartate (PALA):: Particle features and morphology in relation with alkyl chain lengths

Phospholipid analogues of the anticancer agent PALA (N-phosphonoacetyl-L-aspartate) with varying alkyl chain lengths were synthesized: diC(12)-, diC(14)-, diC(16)-, and diC(18)-PALA. Their aptitude to form vesicles was tested using two different preparation techniques: sonication and extrusion. The particles obtained were characterized from cryogenic temperature transmission electron microscopy imaging, showing a continuous morphological evolution when increasing the alkyl chain lengths. Spherical vesicles were obtained for the smaller chain lengths, which evolve toward disklike vesicles, faceted objects, and flat disk structures for longer chain lengths. This evolution was correlated with the transition temperatures, T-m, from the gel state to the liquid crystalline state, which were independently determined. The sonication method was found to lead to smaller objects and increased particle fragmentation compared to extrusion. Particle size measurements and glucose entrapment experiments provided additional results in good agreement with the previous observations.