Multifunctional di-N-oxide surfactants in fabrication of lipid nanoparticles

A homologous series of dicephalic surfactants, 1,1-bis{[3-(N,N-dimethylamino)ethyl]amido}alkane-di-N-oxides (C_nMEDA), is reported, and their applicability for stabilization of the lipid nanoparticles (solid lipid nanoparticles (SLNs) or nanostructured lipid carriers (NLCs)) is discussed and compared with that of their counterparts, single-head–single-tail 2-alkanoylamino)ethyldimethylamines (C_nEDA). For the SLN formation, solid cetyl palmitate (Crodamol CP-PA-(SG) is applied as the solid lipid, and in the case of NLCs, cetyl palmitate and triglycerides of caprylic/capric are applied as the liquid lipid. Structural parameters of the resulting nanoparticles are characterized by dynamic light scattering, transmission electron microscopy and scanning electron microscopy and thermal behavior by differential scanning calorimetry (DSC). The studied nanoparticles stabilized with dicephalic C_nMEDA had a mean diameter of about 145 nm, whereas the particle size of those stabilized with C_nEDA is around 160 nm. Zeta potential measurements demonstrated a negative charge of all obtained SLNs and NLCs, and their values are between −7 and −20 mV. These characteristics remained unchanged for samples stabilized with C_nMEDA for least 3 months, suggesting good stability. According to the DSC findings, the NLCs stabilized by the tested C_nMEDA had lower values for phase transition temperature, melting enthalpy and the recrystallization index than those obtained for the SLNs. The obtained findings suggest that less ordered crystalline structure is conferred by the inclusion of the liquid lipid. Moreover, the SLNs and NLCs stabilized by dicephalic surfactants constitute more stable products than those stabilized by their linear counterparts.