TY - JOUR
T1 - Nanomaterials fusing with the skin
T2 - Alpha-tocopherol phosphate delivery into the viable epidermis to protect against ultraviolet radiation damage
AU - Saleh, Mais M.
AU - Woods, Arcadia
AU - Harvey, Richard D.
AU - Young, Antony R.
AU - Jones, Stuart A.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Vitamin E (alpha tocopherol, α-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating α-tocopherol (α-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 α-TPO4−1 microspecies predominated in solution, dynamic light scattering measurements showed that α-TP formed nanoaggregates with a median hydrodynamic diameter of 9 nm (Critical aggregation constant, CAC, – 4.2 mM). At 9.0 when the α-TPO4−2 microspecies predominated there was no aggregation. The passage of α-TP nanoaggregates through regenerated cellulose membranes was significantly slower than the α-TP monomers (at pH 9) suggesting that aggregation slowed diffusion. However, a lotion formulation containing the nanoaggregates delivered more α-TP into the skin compared to the formulation containing the monomers. In addition, the nanosized α-TP aggregates delivered 8-fold more active into the stratum corneum (SC) (252.2 μg/cm2 vs 29.5 μg/cm2) and 4 fold more active into the epidermis (85.1 μg/cm2 vs 19 μg/cm2, respectively, p < 0.05) compared to α-T. Langmuir subphase injection studies at pH 7.4 (surface pressure 10 mN m−1) showed that the α-TP nanoaggregates more readily fused with the SC compared to the monomers and the membrane compression studies demonstrated that α-TP fluidised the SC lipids. Together the fusion with the SC and its fluidisation were proposed as the causes of the better α-TP penetration into the skin, which enhanced potential of α-TP to protect from UVR-induced skin damage compared to α-T.
AB - Vitamin E (alpha tocopherol, α-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating α-tocopherol (α-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 α-TPO4−1 microspecies predominated in solution, dynamic light scattering measurements showed that α-TP formed nanoaggregates with a median hydrodynamic diameter of 9 nm (Critical aggregation constant, CAC, – 4.2 mM). At 9.0 when the α-TPO4−2 microspecies predominated there was no aggregation. The passage of α-TP nanoaggregates through regenerated cellulose membranes was significantly slower than the α-TP monomers (at pH 9) suggesting that aggregation slowed diffusion. However, a lotion formulation containing the nanoaggregates delivered more α-TP into the skin compared to the formulation containing the monomers. In addition, the nanosized α-TP aggregates delivered 8-fold more active into the stratum corneum (SC) (252.2 μg/cm2 vs 29.5 μg/cm2) and 4 fold more active into the epidermis (85.1 μg/cm2 vs 19 μg/cm2, respectively, p < 0.05) compared to α-T. Langmuir subphase injection studies at pH 7.4 (surface pressure 10 mN m−1) showed that the α-TP nanoaggregates more readily fused with the SC compared to the monomers and the membrane compression studies demonstrated that α-TP fluidised the SC lipids. Together the fusion with the SC and its fluidisation were proposed as the causes of the better α-TP penetration into the skin, which enhanced potential of α-TP to protect from UVR-induced skin damage compared to α-T.
KW - Delivery
KW - Liposomes
KW - Nanomaterials
KW - Skin
KW - Skin interactions
KW - Stratum corneum
KW - α-Tocopherol phosphate
UR - http://www.scopus.com/inward/record.url?scp=85097890278&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.120000
DO - 10.1016/j.ijpharm.2020.120000
M3 - Article
C2 - 33166585
AN - SCOPUS:85097890278
SN - 0378-5173
VL - 594
JO - INTERNATIONAL JOURNAL OF PHARMACEUTICS
JF - INTERNATIONAL JOURNAL OF PHARMACEUTICS
M1 - 120000
ER -