Abstract
Human skin is dramatically exposed to toxic pollutants such as ozone. To counteract the skin disorders induced by the air pollution, natural antioxidants such as mangiferin could be employed. A formulative study for the development of vesicular systems for mangiferin based on phosphatidylcholine and the block copolymer pluronic is described. Plurethosomes were designed for mangiferin transdermal administration and compared to ethosome and transethosome. Particularly, the effect of vesicle composition was investigated on size distribution, inner and outer morphology by photon correlation spectroscopy, small angle X-ray diffraction, and transmission electron microscopy. The potential of selected formulations as vehicles for mangiferin was studied, evaluating encapsulation efficiency and in vitro diffusion parameters by Franz cells. The mangiferin antioxidant capacity was verified by the 2,2-diphenyl-1-picrylhydrazyl assay. Vesicle size spanned between 200 and 550 nm, being influenced by phosphatidylcholine concentration and by the presence of polysorbate or pluronic. The vesicle supramolecular structure was multilamellar in the case of ethosome or plurethosome and unilamellar in the case of transethosome. A linear diffusion of mangiferin in the case of ethosome and transethosomes and a biphasic profile in the case of plurethosomes indicated the capability of multilamellar vesicles to retain the drug more efficaciously than the unilamellar ones. The antioxidant and anti-inflammatory potential effect of mangiferin against pollutants was evaluated on 3D human skin models exposed to O3. The protective effect exerted by plurethosomes and transethosomes suggests their possible application to enhance the cutaneous antioxidant defense status.
Highlights
Introduction distributed under the terms andIn the 21st century, one of the major environmental risks to human health is represented by air pollution, causing a reduction of life expectancy by almost 2 years on worldwide average [1]
Their composition is based on a central polyoxypropylene block surrounded by two hydrophilic polyoxyethylene blocks, and it confers to pluronics a surfactant character suitable for many pharmaceutical applications [27,28,29]
PC 1.8% resulted in temporary homogeneous ethosomes (P7), undergoing phase separation within 15 days, while a further increase in PC concentration up to 2.7% led to an unstable dispersion (P15), which was subject to sedimentation and phase separation within 2 days (Table 2)
Summary
Introduction distributed under the terms andIn the 21st century, one of the major environmental risks to human health is represented by air pollution, causing a reduction of life expectancy by almost 2 years on worldwide average [1]. The noxious effect of O3 on human skin has been thoroughly investigated in the past decades, demonstrating its interaction with stratum corneum macromolecules (i.e., lipids, proteins) that leads to the production of reactive oxygen species (ROS) and secondary mediators, such as the reactive aldehyde 4-hydroxy-nonenal (4HNE) [6] These oxidative stress mediators can spread the oxidative damage throughout the skin layers and eventually induce the activation of inflammatory pathways, resulting in the release of inflammatory cytokines as interleukins (ox-inflammation) [7,8] that are involved in the development and/or exacerbation of conditions such as atopic dermatitis, skin photoaging, photo carcinogenesis, DNA damage, and cell death [9]. A successful approach based on the cutaneous application of natural antioxidant molecules has been well investigated in the last decades
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