Nanoemulsions Based on Sunflower and Rosehip Oils: The Impact of Natural and Synthetic Stabilizers on Skin Penetration and an Ex Vivo Wound Healing Model

Vegetable oils offer excellent biological properties, but their high lipophilicity limits their bioavailability. This work aimed to develop nanoemulsions based on sunflower and rosehip oils and to evaluate their wound-healing activity. The influence of phospholipids of plant origin on nanoemulsions’ characteristics was investigated. A nanoemulsion prepared with a mixture of phospholipids and synthetic emulsifiers (Nano-1) was compared with another prepared only with phospholipids (Nano-2). The healing activity was evaluated in wounds induced in human organotypic skin explant culture (hOSEC) based on histological and immunohistochemical analysis. The hOSEC wound model was validated, showing that high nanoparticle concentration in the wound bed interferes with cell mobility and the ability to respond to the treatment. Nanoemulsions were 130 to 370 nm, with a concentration of 10(13) particles/mL, and a low potential to induce inflammatory processes. Nano-2 was three times larger than Nano-1 but less cytotoxic and could target the oils to the epidermis. Nano-1 permeated intact skin to the dermis and showed a more prominent healing effect than Nano-2 in the hOSEC wound model. Changes in the lipid nanoemulsion stabilizers impacted the cutaneous and cellular penetration of the oils, cytotoxicity, and healing kinetics, resulting in versatile delivery systems.