PUFECBENE®: A microencapsulated pterostilbene with enhanced bioavailability for skin depigmentation

Pterostilbene, a bioactive compound with multifaceted therapeutic potential, has garnered significant interest in cosmetic applications for its depigmentation properties. However, its clinical utility is limited by poor aqueous solubility and bioavailability. To address this, we developed PUFECBENE®, a novel microencapsulated formulation containing 5 % pterostilbene (the rest are 30 % aqua, 48.5 % glycerin, 10 % caprylic/capric triglyceride, 3 % hydrogenated lecithin, 2 % ascorbyl tetraisopalmitate, 1 % pentylene glycol, and 0.5 % 1,2-hexanediol), and measured its particle size and zeta potential using laser diffraction particle analyzer and evaluated its efficacy against pure pterostilbene using in vitro melanocyte and in vivo zebrafish embryo models. PUFECBENE® exhibited uniform aqueous dispersion with a hydrodynamic diameter of 121.72 ± 1.68 nm, a zeta potential of −65.1 ± 0.15 mV, and a transmittance of 80.64 ± 0.062 %. The cytotoxicity assay showed that PUFECBENE® exhibited no cytotoxicity in melanocytes at concentrations ≤ 1.25 µg/mL, while pure pterostilbene was non-toxic up to 3.13 µg/mL. Melanocyte assays demonstrated that 1.25 µg/mL PUFECBENE® reduced melanin synthesis by 57.05 ± 4.09 %, comparable to pure pterostilbene (57.58 ± 0.76 % at 3.13 µg/mL), and immunostaining revealed a 3.36-fold increase in LC3-II (autophagosome marker) and significant LC3-II/Pmel17 (Pmel17 is a melanosome-specific protein) co-localization, indicating autophagy-mediated melanosome degradation. Zebrafish embryos treated with PUFECBENE® (0.5 µg/mL) showed 99.30 ± 3.44 % melanogenesis inhibition, outperforming pure pterostilbene (8.95 ± 7.19 % at 0.5 µg/mL). PUFECBENE® exhibited a 50-fold enhanced in vivo potency relative to pure pterostilbene while retaining comparable in vitro efficacy, highlighting the critical role of bioavailability optimization and in vivo analysis in translating in vitro findings to formulation applications. This highlights the success of microencapsulation in enhancing bioavailability and depigmentation activity, positioning PUFECBENE® as a promising candidate for advanced cosmetic formulations targeting hyperpigmentation.