MACROPHAGE MEDIATED DRUG DELIVERY TO TUMOUR CELLS IN VITRO

There are a number of problems associated with cancer therapy. These include the toxic side-effects associated with clinically used anticancer agents and metastases, which can still develop to form secondary tumours even after a primary tumour has been successfully treated. To minimise both of these problems, methods are being developed to target anticancer drugs to both primary and secondary tumours in order to kill all cancer cells, whilst minimising exposure of normal tissues to such cytotoxic drugs. Since macrophages are involved in the normal physiological response to cancer cells, and have been shown to be actively recruited to some tumours, it was decided that the macrophage might prove a useful vehicle for delivering anticancer drugs directly to some, (or all) site(s) of tumour growth in cancer patients. The work outlined in this thesis describes invitro studies to determine the potential of the macrophage as a drug delivery device. The work was carried out using non-cytotoxic fluorescein derivatives as model anticancer drugs, and two copper coordination compounds , Cu II bis (3,5, diisopropyl salicylate), and Cu II bis (ethyl N-benzyl, 4-hydroxy, 5-oxo, 3-pyrroline, 3-carboxylate). It was found that by encapsulating fluorescein within liposomes, and incubating these liposomes with macrophages, the formulations of the MLVs used altered both the uptake and release of fluorescein by the macrophages. The physicochemical properties of the copper complexes and the MLV formulations used to load the Cu complexes into the macrophages, both altered the cytotoxicity of the macrophages when incubated with cancer cells. These findings indicate that macrophages can be used in vitro to deliver anticancer agents to allogeneic transfomed cell lines. Based on these findings work is to be started to assess the potential of such a system using in vivo models. The work described in this thesis forms the basis of British Patent Application Number 8912294.9 (1991).

Name dc:type.qualificationname

PhD

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

De Montfort University

Year dc:date.issued

1992

Author dc:creator

• Wilson, Christopher James

Licence

• https://dora.dmu.ac.uk/bitstreams/17b34e30-4092-48bd-959b-0d7da5737e2c/download