Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.769949
Title: Delivery of tocopherol phosphate nanomaterials into the skin to protect against ultraviolet radiation
Author: Saleh, Mais Majed Urabi
ISNI:       0000 0004 7660 2219
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2019
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Topically applied vitamin E (α-tocopherol, α-T) can provide protection from ultraviolet radiation induced skin damage and photoaging. However, α-T is oxidized and due to its hydrophobicity it is not easily delivered into viable skin layers where it elicits its photo-protective effect. Alpha-tocopherol phosphate (α-TP), a chemically stable, water-soluble derivative of α-T, could have similar effects as α-T as well as it may be able to more easily reach epidermis. The aim of this thesis was to investigate the skin penetration of α-TP and its photoprotection in vitro. At concentration of 35 mM, α-TP was found to form aggregates with 9 nm hydrodynamic size at a critical aggregation concentration of 4.2 mM when dissolved in 20% ethanol, 20% propylene glycol, 60% tris buffer at pH 7.4. The AFM images showed that at low concertation's (~1 mM), α-TP formed spherical liposomes (diameter of 50 nm, height of 17 nm) and at high concentrations (6 mM) α-TP formed rods (diameter of 300-570 nm, height of 12 nm). The α-TP nanomaterial at pH 7.4 showed a 5-fold higher total skin deposition than α-T. In stratum corneum (SC) lipid monolayer model, the mean molecular area (MMA) per molecule of pure SC lipids at surface pressure of 30 mN/m (30.18 A2/molecule) increased with the addition of 30% α-TP (38.12 A2/molecule), this may be due increase the repulsive forces upon increasing the percentage of α-TP and thus weaken the attractive forces between SC lipids head groups and disrupt their packing. The 24 h pre- incubation of HaCaT keratinocytes with α-TP in low serum media significantly suppressed the cell viability reduction induced by UVA1 (226 J/cm2) by 14% compared to irradiated vehicle control and whereas α-T did not. In vitro α-TP displayed weak antioxidant activity using the DPPH and ORAC assay, but the radical-scavenging activity in HaCaT keratinocytes using pre-irradiation treatment with 100 μM α-TP significantly reduced the ROS generation by ~ 24% compared to the irradiated vehicle control. Adding SLN to the α-TP topical formulation to mimic sunscreen products enhanced the release of α-TP from a 2% lotion and 2% gel by 2-fold and 11-fold, respectively possibly by deaggregation. The α-TP could be delivered into the viable epidermis where it showed photoprotective effects and it seemed feasible to include the α-TP in topical sunscreen (e.g. SLN) formulation to add or maximize the protection.
Supervisor: Jones, Stuart Allen ; Young, Antony Richard ; Harvey, Richard Douglas Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.769949  DOI: Not available
Share: