Albassam, Lulwah; (2025) Selenium nanoparticles: exploration of anti-oxidant properties for potential ocular applications. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Oxidative stress plays a critical role in developing chronic ocular conditions like cataracts. Surgery is the only effective method for treating cataracts, and there is an urgent need to explore ways to slow the progression of cataracts. Selenium nanoparticles (SeNPs) have garnered significant attention to suppress oxidative stress. The state of the art in this field is first introduced in Chapter 1. In Chapter 2, SeNPs were fabricated via chemical reduction methods in the presence of ascorbic acid and tocopherol poly(ethylene glycol) succinate (TPGS), with the synthetic method varied to obtain NPs in different size ranges. The resultant TPGS-SeNPs were examined by a range of characterisation techniques, including dynamic light scattering (DLS), infrared (IR) spectroscopy, transmission electron microscopy, and X-ray diffraction. DLS confirmed the fabrication of nanoparticles of different sizes via different fabrication routes, with those measuring 44 nm exhibiting some colloidal stability. IR spectroscopy identified characteristic peaks indicating TPGS on the surface and the presence of residual ascorbic acid. TEM revealed the NPs to have spherical morphology and a narrow size distribution. X-ray diffraction patterns displayed broad haloes indicative of amorphous systems in most cases. Antioxidant activity was evaluated using a DPPH assay to measure scavenging capacity, with the results indicating that the TPGS-SeNPs exhibit a concentration dependent antioxidant activity. The optimal size of the SeNPs was found to lie within the range of 40 ± 5 nm, based on cytotoxicity data from arising retinal pigment epithelia (ARPE) cells. Chapter 3 explores the in vitro functionality of the lead SeNPs from Chapter 2 in more detail. Additional cytotoxicity studies were performed both on a human lens epithelial cell line (HLE) and APRE-19 cells. Cytotoxicity studies using the Presto blue assay and live dead imaging were used to determine a potentially safe effective dose of ≤ 0.4 μg/mL. Glutathione peroxidase levels were then evaluated in HLE cells and were found to be significantly higher in TPGS-SeNP 4 treated cells compared to untreated controls or those given a solution selenomethionine treatment. Thioredoxin reductase enzyme levels were also higher in TPGS-SeNP treated cells. On the other hand, glutathione, lipid peroxidation and catalase mimetic assays showed no difference between treated and untreated cells. The selective effects on antioxidant pathways indicate that TPGS-SeNPs mainly enhance enzymatic antioxidant defences over non-enzymatic ones in lens epithelial cells. This suggests that TPGS-SeNPs may provide targeted protection against oxidative stress via the upregulation of GPx and TrxR. However, the absence of effects on other antioxidant systems indicates that a complementary approach may be required for comprehensive protection against cataract formation. In Chapter 4, onward formulation of the SeNPs was undertaken. SeNPs were loaded into two different molecular weight hyaluronic acid-tyramine hydrogels (30-50 kDa and 200-400 kDa) to respectively generate a topical hydrogel and injectable gel. The permeation of the topical hydrogel was assessed using a parallel artificial membrane permeability assay for corneal permeation, and it was found that both free SeNPs and those embedded in the gel demonstrated effective permeation with comparable permeability coefficients (approximately ~2x10⁻5 cm/s). In-vitro release experiments using an ocular rig model indicated that the injectable SeNPs-loaded hydrogel formulation displayed a prolonged release profile, with approximately 10.5% cumulative release over 10 days following non-Fickian release kinetics (n = 0.6699). The thesis finishes with overarching conclusions and some suggestions for future work presented in Chapter 5.

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