Abstract
Oxidative stress, triggered by UV radiation, is one of the major causes of free radical-associated disorders, such as skin cancer. The application of natural compounds (NCs) with antioxidant effects can attenuate free radicals’ accumulation and, therefore, provide a strategy for skin care and cancer prevention. In this work, three natural compounds, naringenin, nordihydroguaiaretic acid (NDGA), and kaempferol, were encapsulated into nanostructured lipid carriers (NLCs) aiming for the development of a formulation for cutaneous application with antioxidant properties. For the experiments, different formulation parameters were evaluated to optimize the NLCs that showed a diameter around 200 nm, which is an adequate particle size for incorporation in cosmetics. Transmission electron microscopy (TEM) analysis confirmed the NLCs’ typical spherical morphology. Encapsulation efficiency (EE) and loading capacity (LC) values revealed an effective production process, with EEs over 90% and LCs near the maximum value. The developed NLCs revealed a prolonged in vitro release of the natural compounds. The NLCs were stable under storage conditions, maintaining their psychochemical characteristics for 30 days. Additionally, they did not show any physical instability in accelerated stability studies, which also suggests long-term stability. Finally, the NCs antioxidant activity was evaluated. Interestingly, the NDGA and kaempferol mixture provided an antioxidant synergic effect. The NLC formulations’ cytotoxicity was tested in vitro in immortalized human keratinocytes (HaCaT). In addition, putative antioxidant effects of the developed NLC formulations against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress were studied, and the NDGA-loaded NLC was revealed to be the one with the most protective effect. Therefore, we concluded that the naringenin, NDGA, and kaempferol incorporation into NLCs constitutes a promising strategy to increase their bioavailability and delivery to the skin.
Highlights
Skin cancer, the most common cancer type worldwide, is the out-of-control growth of abnormal cells in the epidermis, triggered by unrepaired DNA damage that leads to mutations [1]
This study proved the feasibility of the selected nanostructured lipid carriers (NLCs) formulations to be a drug-delivery system for the selected natural compounds (NCs), since they maintained stability for to up to 6 months
The developed NLCs maintained their characteristics over 30 days, revealing stability during storage
Summary
The most common cancer type worldwide, is the out-of-control growth of abnormal cells in the epidermis, triggered by unrepaired DNA damage that leads to mutations [1]. The damaging UV radiation effects can be classified as direct or indirect (immunosuppression, inflammatory response, and oxidative stress). Free radicals, such as reactive oxygen species (ROS), can cause indirect damage to cellular components, and growing evidence has suggested that increased ROS levels can induce malignant cell transformation [3,4,5,6,7]. UV radiation exposure can overcome the endogenous skin protection, which is why the application of endogenous antioxidants is crucial to overcome the oxidative stress caused by an imbalance between ROS and defense mechanisms [8,9,10,11]. Natural compounds (NCs) are gaining increased attention due to their pharmacological health-benefitting properties, including antioxidant activity
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