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    Nanomaterials fusing with the skin: Alpha-tocopherol phosphate delivery into the viable epidermis to protect against ultraviolet radiation damage

    Year: 2021

    Journal: Int. J. Pharm., Volume 594, FEB 1

    Authors: Saleh, Mais M.; Woods, Arcadia; Harvey, Richard D.; Young, Antony R.; Jones, Stuart A.

    Organizations: University of Jordan

    Keywords: Nanomaterials; alpha-Tocopherol phosphate; Skin; Stratum corneum; Liposomes; Skin interactions; Delivery

    Vitamin E (alpha tocopherol, alpha-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating alpha-tocopherol (alpha-TP) to form a provitamin, improved its interactions with skin, its passage into the tissue, and thus its ability to protect the skin from ultraviolet radiation (UVR) damage. At pH 7.4, when the alpha-TPO4-1 microspecies predominated in solution, dynamic light scattering measurements showed that alpha-TP formed nanoaggregates with a median hydrodynamic diameter of 9 nm (Critical aggregation constant, CAC, - 4.2 mM). At 9.0 when the alpha-TPC4 2 microspecies predominated there was no aggregation. The passage of alpha-TP nanoaggregates through regenerated cellulose membranes was significantly slower than the alpha-TP monomers (at pH 9) suggesting that aggregation slowed diffusion. However, a lotion formulation containing the nanoaggregates delivered more alpha-TP into the skin compared to the formulation containing the monomers. In addition, the nanosized alpha-TP aggregates delivered 8-fold more active into the stratum corneum (SC) (252.2 mu g/cm(2) vs 29.5 mu g/cm(2) ) and 4 fold more active into the epidermis (85.1 mu g/cm(2) vs 19 mu g/cm(2), respectively, p < 0.05) compared to alpha-T. Langmuir subphase injection studies at pH 7.4 (surface pressure 10 mN m(-1)) showed that the alpha-TP nanoaggregates more readily fused with the SC compared to the monomers and the membrane compression studies demonstrated that alpha-TP fluidised the SC lipids. Together the fusion with the SC and its fluidisation were proposed as the causes of the better alpha-TP penetration into the skin, which enhanced potential of alpha-TP to protect from UVR-induced skin damage compared to alpha-T.
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