Preparation and properties of vesicles formed from phospholipid analogues of N-(phosphonoacetyl)-L-aspartate (PALA) by sonication or extrusion: Transition temperature, particle size, glucose entrapment, and P-31 NMR

We characterize here the ability of new amphiphilic compounds to form vesic les that could potentially be used as vectors for therapeutical application s. These compounds are derived from N-phosphonoacetyl-L-aspartate (PALA), a potential antitumoral agent. Vesicular dispersions of phospholipid analogu es of PALA with different alkyl chain lengths (diC(12)-, diC(14)-, diC(16)- , and diC(18)-PALA), which had been previously synthesized, are tested from different points of view. Two kinds of preparation methods are compared: s onication; extrusion. The two preparation methods resulted in important dif ferences in the properties of the dispersions which confirmed the conclusio ns of a previous investigation from cryo-TEM imaging. The results of fluore scence polarization experiments, performed either with the pure compounds o r their mixtures with lecithins or cholesterol, indicated that the transiti on temperature T. can be modulated if it is required for the applications. The sonicated particles showed smaller size and much lower glucose encapsul ation than the extruded particles. In both cases these properties are only weakly depending on the amphiphile alkyl chain lengths. The glucose permeab ility has appeared to considerably increase (lower encapsulation) at T > T- m. The effect of Mn2+ on the P-31 NMR signal intensity suggested that unila mellar vesicles are coexisting with other types of particle in case of extr usion, whereas in case of sonication only few and less stable vesicles are present, in agreement with the preceding observations.