Biocompatible Lyotropic Nanocarriers for Improved Delivery of Ascorbyl Tetraisopalmitate in Skincare

Ascorbyl tetraisopalmitate (VC-IP) is a novel form of ascorbic acid characterized by reduced water solubility due to complete acylation with palmitate. This study investigated the potential cosmetic application of VC-IP when encapsulated in lyotropic liquid crystal nanoparticles (VC-IP LCNPs) by using a high-pressure homogenization (HPH) method. The particle size, zeta potential, and polydispersity index (PDI) of the obtained VC-IP LCNPs were determined as 158.8 ± 3.2 nm, −35.1 ± 2.8 mV, and 0.12 ± 0.02, respectively. The drug loading (DL%) of the VC-IP LCNPs was approximately 35.1%. Morphological changes in LCNPs, transitioning from a sponge phase to vesicles, confirmed the successful loading of VC-IP, as demonstrated by transmission electron microscopy (Cryo-TEM) and small-angle X-ray scattering (SAXS) experiments. The sustained release of VC-IP was also observed through the Franz transdermal diffusion test, indicating that VC-IP LCNPs facilitated the sustained-release effect of VC-IP into the skin. VC-IP LCNPs exhibited good biocompatibility, showing nontoxicity to HaCaT cells and zebrafish embryos. Raman distribution imaging confirmed that VC-IP successfully penetrated the stratum corneum and reached the dermis. In assessments of whitening effects, VC-IP LCNPs significantly the reduced reactive oxygen species (ROS) content in zebrafish and melanin areas in the heads of zebrafish. Furthermore, VC-IP LCNPs effectively inhibited tyrosinase activity and the proliferation of A375 cells compared with pure VC-IP. Additionally, VC-IP LCNPs significantly reduced the melanin area in the heads of zebrafish. Therefore, the developed VC-IP LCNPs present a promising carrier for the enhanced application of active ingredients, such as VC-IP in whitening products.