| Summary: | The application of inorganic chemistry to medicine is a rapidly developing
field, and novel therapeutic and diagnostic metal complexes are now having
an impact on medical practice. The family of platinum-containing medicinal
agents used for the chemotherapy of malignancies ranks among the most
potent types of anticancer drug in present use. While highly potent against
many cancers, cisplatin like other anticancer drugs suffers from virtually all
of the clinical limitations observed with metal-free antitumor agents in
current clinical use, most notably toxic side effects and a propensity for
eliciting drug resistance in the cancerous cell. In an effort to increase the
effectiveness of chemotherapy, one of the techniques in, use involves the
binding of, the monomeric anticancer drug systems to water-soluble,
biocompatible and biodegradable polymeric carriers. The interest in, and
use of, polymers as drug delivery systems has received considerable
attention worldwide; and this technique was utilized in this project.
In the present project monomers bearing suitable side groups (aspartic and
glycolic acid) for platinum drug anchoring in a chelating form were
synthesized. These monomers were incorporated into the polymer
backbone as side chain units. Functionalized polyaspartamides and
polyamidoamines were water-soluble carriers used in this project, and they
were obtained by condensation and Michael addition polymerization.
Leaving group ligands (dicarboxylato, carboxylatohydroxylato, and
dihydroxylato) were used to anchor the platinum drug to the polymer
backbone. The platinum content of conjugates was in the range of 0.92 % -
18.15 %. A certain number of the resulting conjugates were bio-evaluated in vitro for
their antiproliferative activities against the HeLa, Colo 320 DM and MCF 7
human cancer cell lines, while the corresponding carriers were in vitro
tested for toxicity against resting and stimulated human lymphocyte cell
lines. For 50 % cell growth inhibition, concentrations varying from 0.000044
to 9 μg/mL Pt for conjugates and 4 to >50 μg/mL for carriers were reported.
|
|---|
