Lipid nanostructures for antioxidant delivery: A comparative preformulation study

This investigation aims to generate new lipid nanoparticles for cutaneous antioxidant delivery. Indeed, several molecules, such as α-tocopherol and retinoic acid, have been shown to improve skin condition and even counteract the effects of exogenous challenges such as smoking on skin aging. Particularly solid lipid nanoparticles and nanostructured lipid carriers have been investigated. Solid glyceride lipids, such as tristearin, precirol, compritol and suppocire have been employed in the absence and in the presence of miglyol. A comparative study has been conducted in order to evaluate the effect of different lipid compositions on presence of agglomerates, dimensional distribution, morphology and encapsulation efficiency of lipid nanoparticles. After production of nanoparticles by ultrasound homogenization, their dimensional distribution was measured by photon correlation spectroscopy and evaluated until 90 days from production. Since nanostructured lipid carriers enabled to reduce the agglomerate formation and to control their dimensional stability with respect to solid lipid nanoparticles, they have been selected for antioxidant encapsulation. Once nanostructured lipid carriers have been produced in the presence of α-tocopherol and retinoic acid, their external and inner structure have been characterized by cryogenic transmission electron microscopy and x-ray spectroscopy respectively. Antioxidant encapsulation efficiency was evaluated by HPLC upon disaggregation of nanostructured lipid carriers. Apart from suppocire, that lead to formation of spherical vesicles, the other lipids resulted in irregular shaped nanoparticles. A doubling in the lipid phase amount enabled to double the α-tocopherol loading within the nanoparticles, controlling the drug stability up to 3 months. To evaluate the protective properties of the nanostructured lipid carriers loaded with α-tocopherol, human skin explants pretreated with nanostructures were exposed to cigarette smoke, afterwards protein levels of the stress inducible enzyme heme oxygenase were analyzed in skin homogenates. Interestingly, it was found that the pretreatment avoided heme oxygenase upregulation, suggesting a protective effect of the nanoparticles.