Transdermal Penetration of Photoluminescent Nanoparticles in Human Skin
Applications of nanomaterials in cosmetics and pharmaceutical industries raise safety concerns due to their potential penetration into skin. Skin outermost layer, stratum corneum (SC), is an effective barrier for extraneous compounds stopping these materials from entering viable epidermis (VE) and concomitantly systemic circulation of the body. At the same time, transdermal delivery of drugs and cosmetic ingredients critically relies on the enhanced penetration of nanomaterials through skin. This thesis addresses both nanotoxicology and transdermal delivery aspects of nanoparticle interaction with skin.
It is consented that ZnO NPs in sunscreens do not penetrate intact skin. However, it has been reported that sunscreens containing ZnO NPs increase zinc ions (Zn2+) levels within VE due to the dissolution of ZnO NPs and releasing Zn species. An excess of zinc (Zn) may be toxic to mammalian cells and organisms, demanding quantitative assessment of Zn accumulation in VE. At the same time, quantification of exogenous trace elements (Zn) in skin, containing exogenous trace elements, is challenging. In order to address this problem systematically, skin absorption of zinc from sunscreen was quantified via an ion coupled plasma mass spectrometry (ICP-MS) and laser-ablation ICP-MS (LA-ICP-MS) techniques. In addition, a sunscreen formulation containing a rare stable isotope of Zn (67Zn) with a natural abundance of 4.04% was used to discriminate sunscreen-derived Zn from endogenous zinc in skin. Assayed concentration of Zn in VE was found to be 1.0 ± 0.3 mg/mL, which was much lower than the potentially cytotoxic labile 67Zn concentrations of 21 – 31 mg/mL. This research speaks strongly in favour of the safety of ZnO NP sunscreens and is expected to be impactful in the field of nanotoxicology.
Precise evaluation and monitoring uptake of trace elements in biological samples is a crucial and challenging task as oftentimes organ tissues and cells contain high concentrations of trace elements naturally, which results in eclipsing background. To push the existing detection limits, an LA-ICP-MS methodology was developed to quantify trace elements, such as zinc stable isotopes exogenously introduced in biological tissues, such as skin. Optimal laser ablation parameters, choice of internal and external calibration standards, and preparation/analysis methods were explored in detail and presented in this Thesis.
Upconversion nanoparticles (UCNPs) are great platform for systematic studies of nanomaterial transport in skin due to their exceptionally high contrast in optical imaging. To quantify effects of these compounds on the permeability of human skin, we applied UCNPs formulated in a chemical penetration enhancer (ethanol-water solution) followed by advanced optical microscopy, LA-ICP-MS and data analysis to demonstrate, for the first time, that ethanol-water solution led to a noticeable penetration enhancement of UCNPs. Furthermore, using an in vitro tissue engineering model of non- cornified epidermis, we showed that allegedly cytotoxic polyethyleneimine-coated UCNPs were nontoxic within the accepted safety levels.
This work is structured as a thesis by publications, with two introductory chapters, followed by one published paper and two publications, now in submission, to comprise three thesis chapters, and a chapter drawing conclusions and outlook of this PhD project.
