Developing lipid nanocapsules therapeutics for skin cancer

Abstract

Skin cancer remains a significant global health burden, necessitating innovative approaches to improve treatment efficacy and patient outcomes. This thesis explores lipid nanocapsules (LNCs) as advanced drug delivery systems to address challenges associated with conventional therapies, such as poor drug solubility, limited cellular uptake, and suboptimal pharmacokinetics. A comprehensive study was conducted to develop, optimise, and evaluate LNC formulations for photothermal therapy (PTT) using indocyanine green (ICG) and for delivering poorly soluble drugs, including imiquimod (IMD).The research systematically investigates and evaluates the behaviour of LNCs across various drug delivery and therapeutic scenarios. The research first focuses on optimising IMD-loaded LNCs by exploring modifications in the core and shell composition to improve encapsulation efficiency and biocompatibility. The findings demonstrated that oleic acid-enriched LNCs significantly enhanced drug loading capacity, while alternative surfactants minimised cytotoxicity. Then we investigated the cellular uptake and intracellular trafficking of LNCs, revealing that macropinocytosis is the principal endocytic pathway in melanoma cells. Our optimised Span80-containing LNCs (LNC100-S8) maintain lower cytotoxicity while achieving increased cellular uptake. These insights inform the design of more precise and effective nanocarrier systems. Finally, we evaluated the photothermal performance of indocyanine green (ICG)-loaded LNCs (ICG-LNC100-S8), revealing superior photothermal conversion efficiency and effective tumour ablation in 3D melanoma spheroid models. The integration of nanotechnology and photothermal therapy showcases the synergistic potential of LNC-based platforms in treating skin cancer.The findings underscore the transformative potential of LNCs in improving therapeutic delivery, particularly for skin cancer. This work contributes to the field of nanomedicine by advancing our understanding of LNC properties and their application in cancer therapy.

Thesis is embargoed until 31 July 2027.

Date of Award	Jul 2025
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Wafa Al-Jamal (Supervisor) & Taher Hatahet (Supervisor)