Design of solid lipid nanoparticles for skin photoprotection through the topical delivery of caffeic acid-phthalimide

Exposure of the skin to ultraviolet (UV) radiation is associated with many pathological conditions such as premature aging and skin cancer. Furthermore, members of Nicotinamide Adenine Dinucleotide Phosphate-oxidase (NADPH oxidase or NOX) enzyme family can produce UV-induced reactive oxygen species (ROS), even after cessation of radiation exposure. The caffeic acid-phthalimide (CF) compound is a potent antioxidant, which reduces the generation of ROS. However, its high lipophilicity may hamper its permeation through the skin. Solid lipid nanoparticles (SLNs) can ensure close contact and increase the amount of drug absorbed into the skin. The present work aims to develop and optimize SLNs containing CF to achieve enhanced skin photoprotection along with antioxidant and anti-aging effects. SLNs were prepared by the hot homogenization method using Compritol 888 ATO as lipid matrix, and Tween 80 and Pluronic® F-127 as surfactants to stabilize the nanoparticle dispersion. The particles had high stability for at least 30 days. Physicochemical characterizations of the selected SLNs formulations showed sizes in the range 150-180 nm, polydispersity index (PDI) of 0.2, and a negative zeta potential (≅ -25  mV). The SLNs had high CF entrapment efficiency (96-97 %) and showed a controlled drug-release profile. The in vitro study revealed low cytotoxic properties of CF-loaded SLNs towards fibroblasts and a photoprotective effect, reflected from the increased viability of UVB-irradiated fibroblasts treated with CF-SLNs. Moreover, the CF-SLNs induced fibroblast migration and closure, showing that these nanosystems offer not only biological photoprotection, but also stimulate wound healing.