Development and characterisation of disulfiram-loaded PLGA nanoparticles for the treatment of non-small cell lung cancer

Najlah, Mohammad and Ahmed, Zahima and Iqbal, Mohammed and Wang, Zhipeng and Tawari, Patrica and Wang, Weiguang and McConville, Christopher (2016) Development and characterisation of disulfiram-loaded PLGA nanoparticles for the treatment of non-small cell lung cancer. European Journal of Pharmaceutics and Biopharmaceutics. ISSN 0939-6411 (Accepted)

[img]
Preview
Text
Accepted Version
Available under the following license: Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Preview
[img] Other (Acceptance email)
Other
Restricted to Repository staff only

Download (215kB)
Official URL: http://doi.org/10.1016/j.ejpb.2016.11.032

Abstract

Non - Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diag nosed NSCLC. However, DSF is rapidly (4 minutes) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF - loaded PLGA nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model. Here we demonstrate the influence of PLGA polymer, stabilizer loading and molecular weight as well as sonication time on the characteristics, including DSF release and the cytotoxicity of 10% w/w DSF - loaded PLGA nanoparticles. The paper demonstrates that the choice of PLGA as no significant influence on the characteristics of the nanoparticles apart from their DSF release, which is due to the differing degradation rates of the polymers. However, increasing the l oading and molecular weight of the stabilizer as well as the sonication time reduced the size of the nanoparticles , reduced the ir ability to protect the DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxic ity. Additionally, increasing the sonication time resulted in the premature degradation of the PLGA, which increased the permeability of the nanoparticles further decr easing their ability to protect DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity.

Item Type: Journal Article
Keywords: disulfiram, lung cancer, nanoparticles, PLGA
Faculty: Faculty of Medical Science
Depositing User: Dr Mohammad Najlah
Date Deposited: 05 Dec 2016 16:35
Last Modified: 30 Nov 2017 02:02
URI: http://arro.anglia.ac.uk/id/eprint/701255

Actions (login required)

Edit Item Edit Item