Formulation of targeted drug-loaded nanoparticles for lung cancer therapy

Student thesis: Doctoral Thesis

Abstract

The use of combination chemotherapy for treatment of lung cancer has been proven to be more effective than single-agent therapy. Such combination, when used in conjunction with nanoparticle carriers has the potential to effectively deliver the therapeutic payload to the cancer sites with minimal side effects. Small scale production method of liposome in laboratory setting such as thin film hydration requires post-processing steps to achieve desired physical characteristics and upscaling such method would prove to be economically unfeasible. Laboratory scale liposome purification methods such as dialysis and ultracentrifugation also suffer from similar limitation in upscaling. These challenges need to be overcame to streamline liposome production from laboratory to commercial scale whilst maintaining the desired liposome characteristics.In this study, liposomal formulations with varying molarratio of 1, 2-Distearoyl-sn-glycero-3-phosphocholine, 1, 2-Dipalmitoyl-sn-glycero-3-phosphocholine, 1, 2-Distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) and cholesterol were fabricated using microfluidics technique with staggered herringbone mixer. Desired liposomal formulations were obtained by manipulating fabrication characteristics such as total flow rate (TFR) and aqueous-to-lipid flow rate ratio. Selected stable liposomal formulations were then subjected to entrapment of cisplatin and irinotecan, filter centrifugation and tangential flow filtration (TFF) methods, scaleup fabrication process, entrapment efficiency and release studies, lyophilisation and invitro assay against A549 cells. It was also observed that these stable liposome formulations are suitable for entrapment of both cisplatin and irinotecan and demonstrated higher cytotoxicity against A549 cancer cells in comparison with their free drug counterparts.TFF method was found to be more effective in purification and concentrating large volume of liposomal suspension. Scaling up fabrication volume exhibited no significant impact on the physical characteristics, entrapment efficiencyand entrapped material release characteristics of the liposomes. The results of this study demonstrated the feasibility, scalability and modularity of dual-loaded irinotecan and cisplatin in a liposomal system and also its higher efficacy against A549 cancer cells, paving the way for the use of this liposomal system for lung cancer therapy.
Date of Award30 Sep 2020
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorGavin Halbert (Supervisor) & Dimitrios Lamprou (Supervisor)

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