Towards a targeted formulation for treatment of small cell lung cancer

Akbar, Mohammad (2016) Towards a targeted formulation for treatment of small cell lung cancer. Doctoral thesis, University of East Anglia.

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Abstract

Lung cancer is one of the most common cancers with small lung cancer (SCLC) representing 14% of the total lung cancer incidence. It is the major cause of cancer death in the UK. Most patients present with extensive disease, which is difficult to treat with the standard chemotherapy. Liposome-based approach provides a tool for improving treatment outcomes. Liposome is versatile tool, with tuneable features such as composition, size and charge. It can be used as a targeting therapy.
The aim of this study was to synthesis a targeted liposomal drug delivery system for SCLC that enhances delivery to GRPR+ cells through conjugation with an antagonist peptide, cystabn. To do that, the receptor expression evaluated in the SCLC cell line (H345) and NSCLC cell line (A549) by indirect antibody detection using flow cytometed. The cystabn peptide was synthesised using Fmoc-SPPS and coupled to DSPE-PEG2000-Maleimide. The dyalised product was characterised by HPLC, UV and MALDI-TOF MS. PEG-stabilised control liposomes were prepared using the thin film hydration method and characterized by DLS. A targeted liposome formulation was prepared by including 1 mole % DSPE-PEG2000-cystabn in the control formulation. Fluorescent liposomes include 1 mole % DHPE-fluorescein. Cell uptake was measured on by flow cytometer.
Uniform targeted liposome formulation were prepared with good stability. The cystabn peptide showed no growth stimulation in H345 and A549 cells, both of which have been shown to express GRP-R to varying extents. Uptake of targeted liposomes into SCLC cells was equivalent for control and targeted formulations. This indicates that the current formulation approach is inappropriate for the preparation of targeted liposomes.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Jackie Webb
Date Deposited:	13 Dec 2016 15:53
Last Modified:	13 Dec 2016 15:53
URI:	https://ueaeprints.uea.ac.uk/id/eprint/61696
DOI:

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