Nanostructured Lipid Carriers (NLCs) for Cancer Therapy via Pulmonary Drug Delivery

Apostolou, M (2025) Nanostructured Lipid Carriers (NLCs) for Cancer Therapy via Pulmonary Drug Delivery. Doctoral thesis, Liverpool John Moores University.

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Abstract

Lung cancer has been a leading cause of cancer-related deaths worldwide over the past years, creating the necessity for novel therapeutic approaches that can enhance drug delivery efficiency while minimising systemic toxicity. This thesis focuses on the development and optimisation of nanostructured lipid carriers (NLCs) for pulmonary delivery of trans-chalcone (TC), a chemotherapeutic agent. NLCs were prepared using various combinations and amounts of solid and liquid lipids, surfactant, and co-surfactant to achieve optimal physicochemical properties, such as particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and drug loading (DL%). Stability studies under various conditions, i.e., fridge temperature at 5±3°C, room temperature at 25±2°C and accelerated temperature at 40±2°C, further validated the robustness of these formulations.Post-stability, the best TC-NLC formulations were selected and further evaluated for aerosolisation performance using two different nebulisation devices (i.e., air-jet nebuliser and vibrating mesh nebuliser) for TC-NLC suspension formulations; and a mono dose inhaler (i.e., dry powder inhaler (DPI)) for the spray-dried (SD) SD-TC-NLC powder formulations. The spray drying technique was performed using two different carriers, lactose monohydrate (LAC) and trehalose dihydrate (TRE), in order to assess their differences and suitability for SD-TC-NLC formulations. The study identified the most promising formulations based on their PS distribution, production yield, and effective pulmonary deposition profiles. Cytotoxicity studies conducted on MRC-5, MRC-5 SV2, and A549 cell lines demonstrated that the optimised TC-NLC suspension formulations, i.e., 4B-TC-NLCs, 5B-TC-NLCs, 13C-TC-NLCs, 13D-TC-NLCs and 16E-TC-NLCs, exhibited selective toxicity towards cancer cells with minimal effects on normal cells, with one SD-TC-NLC, i.e., 13D-LAC-TC-NLCs and one surface modified (SM) SM-TC-NLC formulation, i.e., 13D-POE-TC-NLCs showing enhanced cytotoxicity compared to the corresponding TC-NCL suspension formulations and the plain TC. An advanced characterisation technique such as Fourier transform infrared (FTIR) spectroscopy was also employed to confirm the molecular stability and interactions within the NLC formulations.The findings suggest that NLCs, particularly those optimised for pulmonary delivery and those which have been SD or SM, offer a viable and effective alternative to traditional chemotherapeutic methods, providing targeted drug delivery with reduced side effects, making them more patient-friendly.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	NLCs; pulmonary drug delivery; drug delivery systems; cancer therapy; lung cancer
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy and Biomolecular Sciences
Date of acceptance:	23 April 2025
Date Deposited:	08 May 2025 14:19
Last Modified:	08 May 2025 14:19
Supervisors:	Khan, I, Assi, S and Fatokun, A
URI:	https://researchonline.ljmu.ac.uk/id/eprint/26274

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