Polymeric Nanocapsules Containing Kojic Acid Dipalmitate and Rosehip Oil: Development and Evaluation of Preliminary Efficacy and Safety for Skin Whitening

Polymeric nanocapsules associated with kojic acid dipalmitate (KDP) and rosehip oil can be a strategy to obtain high-performance skin whitening/lightning formulations. Nanocapsules containing 0.1% of KDP and 5% of rosehip oil were developed with different polymers (Eudragit RS100, Eudragit S100, poly-(ε-caprolactone) (PCL) and poly-(d,l-lactide-<i>co</i>-glycolide) (PLGA)) to limit the contact of KDP with the external media and avoid its degradation. The nanocapsules had a diameter of less than 200 nm, with suitable size distribution, a pH range between 2.5 and 5.0, a KDP content of 0.9 mg/mL and an encapsulation efficiency above 99%. The zeta potential was positive for the Eudragit RS100 nanocapsules and negative for the other nanocapsules. The PLGA nanocapsules were selected due to better stability results, since there was no decay in KDP content after 180 days (refrigerated storage). The in vitro skin permeation assay showed that KDP reaches the epidermis. This formulation showed in vitro antioxidant activity through both the DPPH assay and the β-carotene/linoleic acid assay when used at 25 μg/mL of KDP, with higher activity than a kojic acid solution (KDP correspondent concentration) and, at 13.75 μg/mL, inhibited tyrosinase in vitro to 17%, significantly greater than the kojic acid solution. A 25% melanin reduction was obtained after normal human epidermal melanocytes (NHEM) were treated with 3.1 μg/mL of KDP. Cytocompatibility was observed after 24 h treatment with up to 6.25 μg/mL of the formulation in fibroblast-like cells (3T3-L1) and up to 3.1 μg/mL in NHEM. Therefore, PLGA nanocapsules containing KDP and rosehip oil have potential for use in skin whitening/lightning formulations.