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

Abstract

This article reports the thermodynamic changes of lipid nanoparticles (LN) upon delivery of lipophilic vitamin E derivatives to the skin. Skin penetration of a- tocopherol (a-T) and a-tocopherol acetate (a-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 calo- rimetry (DSC) have been used to characterize the poly- morphism 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 b' 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 C, and this size range was kept constant for at least 20 days of shelf life. Quantification of a-T and a-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 a-T and a-Ta when delivered via LN was due to the different thermodynamic activity of both actives, i.e., following increased partition coefficient of a-Ta into SC and VE, in comparison to a-T.