Influence of hexadecylphosphocholine (Miltefosine) in phytantriol-based cubosomes: A structural investigation

Abstract

Miltefosine (hexadecylphosphocholine, HePC) is a broad spectrum antimicrobial, anti-leishmanial drug, originally developed as anti-cancer agent. Because of its toxic side effects, several nanotechnology-based formulations have been considered as carriers for HePC. It is clear that the loading efficiency and bioavailability are strongly correlated to structural properties of the considered nanocarries. Therefore, the interplay between the structure stability and the entrapped compounds is worthy of investigation. In the present study, we evaluated the structural properties of phytantriol (PHY) cubosomes prepared in full hydrated conditions in the presence of increasing HePC concentrations. Dynamic Light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS) were used. According to our data, HePC did not influence the nanoparticle average size at least up to 10 mol% HePC/PHY, even if the nanoparticle polydispersity index (PDI) increased by two-fold. On the other side, the nanoparticle inner structure shows a strong drug concentration dependence. Up to 3.5 mol%, the nanoparticles show a bicontinuous Pn3m Cubic internal structure, the lattice parameter of which increases as far as HePC is added to the system. The calculated structural data suggest that the HePC mixing with phytantriol induces a larger hydration capacity of the lipid polar surfaces. For HePC concentrations higher than 7.0 mol%, the internal structure of cubosomes is characterized by the coexistence of Pn3m and Im3m bicontinuous cubic phases, indicating that the swelling of the Pn3m phase arrived at saturation. The calculated number of water molecules per lipid in the cubic unit cell confirms such an indication. The structural parameters derived for the two cubic phases also indicate that HePC influence modify the negative Gaussian surface of the cubosomes.