ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P200. Improving Platinum Chemotherapy Through Controlled and
Targeted Drug Delivery
N. Wheate
Strathclyde Institute of Pharmacy and Biomedical S,University of Strathclyde,27 Taylor Street,G40NR,
Glasgow,United Kingdom
e-mail: nial.wheate@strath.ac.uk
Cisplatin, carboplatin and oxaliplatin are the only three platinum based drugs with wide approval for the
treatment of human cancers [1]. Whilst several new drugs are in various stages of clinical trials including
satraplatin, picoplatin and multinuclear drugs [1], the biggest advances in the coming decade will come from the
development of controlled and targeted drug delivery systems. Over the last 5 years our work has focussed on
macromolecules which can encapsulate mono- and multinuclear platinum complexes and platinum based DNA
intercalators [2-3]. This includes cyclodextrins, calixarenes, cucurbiturils and PAMAM dendrimers. Many of
these macromolecules are able to prevent drug degradation by thiol peptides and proteins and can be used to tune
the cytotoxicity and toxicity of the drugs. In vivo animal trials also demonstrated that one drug delivery vehicle,
cucurbituril was able to nearly double the maximum tolerated dose of a multinuclear platinum drug. The first
phase of our research is nearly complete and we are now examining two-fold drug encapsulation and suitable
targeting groups. In the end, the goal of our research is the development of a targeted platinum drug delivery
system that can specifically recognise and bind cancer cells, thus eliminating many of the side-effect of platinum
drugs from that arise from non-specific cellular attack, and improve drug efficacy.
References:
[1]L. Kelland. The resurgence of platinum-based cancer chemotherapy, Nature Reviews Cancer, 2007, 7, 573-
584.
[2] N. J. Wheate, D. P. Buck, A. I. Day, J. G. Collins, Cucurbit[n]uril binding of platinum anticancer complexes,
Dalton Transactions, 2006, 451-458.
[3] S. Kemp, N. J. Wheate, S. Wang, J. G. Collins, S. F. Ralph, A. I. Day, V. J. Higgins, J. R. Aldrich-Wright,
Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils, Dalton Transactions, 2007,
12, 969-979.
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