Abstract

Cancer is responsible for approximately one out of every six deaths worldwide, making it a significant contributor to global mortality. There are approximately three million people living with cancer in the UK and the number predicted to increase by half a million by 2025. Glioblastoma (GB) is a grade IV brain tumours, it stands as the most prevalent and devastating form of brain tumours. Patients diagnosed with GB have a median survival of only 14.6 months following conventional treatment plan of surgery, radiation and chemotherapy. Passing through the blood-brain barrier (BBB) remain as a challenge when treating GBs, in addition to other limitation of the current treatment. Therefore, there is a need to develop a new carrier system, like nanoparticles (NPs) to improve the drug delivery. NPs can potentially overcome the challenges posed by the BBB, enhance the targeting of glioma stem cells, and reduce the side effects associated with conventional treatments.

This project aims to develop lipid-based NPs using two formulation techniques: high-speed homogenization for nanostructured lipid carriers (NLCs) and microfluidics for lipid nanoparticles (LNPs). The formulations were loaded with epigallocatechin gallate (EGCG), a phytochemical which has anti-cancer properties, aiming to potentially bypass the BBB and target glioblastoma cells.

The developed NPs were assessed for size, polydispersity index, and zeta potential using dynamic light scattering (DLS) Zetasizer. The developed EGCG NLC has a particle size of 174.06 (nm) with a PDI of 0.201, and zeta potential of –4.28 mV, while EGCG LNP has a particle size of 147.96 (nm) with a PDI of 0.261 and a zeta potential of –24.6 mV. The EGCG loaded into the NPs was quantified using a newly developed and validated HPLC method where the NLC total drug was 81.08 % and for the LNP total drug was 79.56 %. Stability studies were conducted over one month on NLC formulations, evaluating physiochemical properties. The EGCG NLC that demonstrated superior results was selected. In colloidal stability study, across various media, water provided the best stability for both EGCG NLC and EGCG LNP formulations.

Future work, evaluation of the efficacy of the developed NPs formulations, in-vitro cell proliferation assay assessment on the U87MG (human glioblastoma cell lines) and SVG P12 (human, non-cancerous foetal glial line) cell lines. This research provides a foundation for future studies aiming to enhance drug delivery to GBs and potentially improve therapeutic outcomes.