Conjugation of squalene to acyclovir improves the interaction for biomembrane models

Differential scanning calorimetry has been used to study the interaction of acyclovir and its prodrug squalenoyl-acyclovir (obtained by conjugation of 1,1’,2-tris-nor-squalene acid (squaleneCOOH) with acyclovir) with biomembrane models made of dimyristoylphosphatidylcholine multilamellar vesicles with the aim to verify if a stronger interaction of the prodrug with respect to the free drug can be obtained. Multilamellar vesicles have been prepared in the presence of increasing molar fractions of acyclovir, squaleneCOOH or prodrug and the effect of the compounds on the thermotropic behavior of vesicles has been researched, revealing no effect of acyclovir but a strong effect of squaleneCOOH and prodrug. To evaluate if acyclovir, squaleneCOOH and prodrug can be absorbed by the biomembrane model, a kinetic experiment has been carried out in which the considered compounds have been left in contact with the biomembrane model and their eventual uptake has been evaluated analyzing the effect on the thermotropic behavior of the biomembrane model. A very small uptake has been revealed for all the compounds. To check the potential use of liposomes as a delivery system for the prodrug, the biomembrane models have been incubated with liposomes loaded with the compounds and the compounds transfer from the loaded liposomes to the unloaded biomembrane model has been followed monitoring the variation of the biomembrane model thermotropic behavior. The results suggest that liposomes could be used to deliver the squalenoyl-acyclovir to the biomembrane model.