Thermodynamic behavior of lipid nanoparticles upon delivery of Vitamin E derivatives into the skin: in vitro studies

This article reports the thermodynamic changes of lipid nanoparticles (LN) upon delivery of lipophilic vitamin E derivatives to the skin. Skin penetration of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-Ta) into and across porcine ear skin was investigated in vitro using tape-stripping test in modified Franz diffusion cells. Wide angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC) have been used to characterize the polymorphism of the solid matrix of LN before and after in vitro skin penetration assay. Cetyl palmitate LN with a loading capacity of 20% of vitamin E derivatives (with regard to the lipid matrix) have shown the typical beta' modification of waxes, with a crystallinity index (%CI) between 30 and 40%. Mean particle size and shelf life stability was assessed by static (laser diffractometry, LD) and dynamic (photon correlation spectroscopy, PCS) light scattering techniques. Submicron-sized LN were produced, i.e., 99% of LN showed a size below 600 nm immediately after production. A mean size between 180 and 350 nm (polydispersity index < 0.25) was obtained for LN stored at both 8 and 22 degrees C, and this size range was kept constant for at least 20 days of shelf life. Quantification of alpha-T and alpha-Ta in the skin using tape-stripping provided a 3.4-fold increase in the level of actives within the stratum corneum (SC) and 1.3-fold increase in the viable epidermis (VE). LN increased skin penetration of both actives, following a cumulative release during 8 h in modified Franz diffusion cells. The differences in the distribution levels observed between alpha-T and alpha-Ta when delivered via LN was due to the different thermodynamic activity of both actives, i.e., following increased partition coefficient of alpha-Ta into SC and VE, in comparison to alpha-T.