Principal Investigator T Hatton
A more effective potential carrier far the anti-cancer drug Doxorubicin is being developed under the supervision of Professor Michael Tan of NTU (up to Jun 2007) and Professor Alan Hatton of MIT,
The chemotherapy drug Doxorubicin. or DOX as the drug is also known, is commonly used to treat a range of cancers. It works by stopping cancer cells from replicating. However DOX is tonic to healthy human cells and can also cause cardiac arrest. The challenge is two-fold: to improve the carrier system for DOX while minimizing the side-effects of DOX.
Polymer-based drug cameras such as Pluronic® co-polymers have been studied extensively as drug delivery vehicles. One of them, Pluronic® P85, is safe for human tissue but its loading capacity or the ability to soak up DOX is very low -- only about 3%. When delivered intraveneously. the side effects of the drug can be severe.
As DOX is cationic, the study experimented with grafting a negatively charged polyacrylic acid (PM) to both ends of the Pluronic®. The PAA graft attracted DOX so effectively that the loading capacity of the new polymer, dubbed Pluronic-b-PAA dramatically improved to 90%.
In addition, the modified carrier had qualities that would enable a finer control in administrating DOX. For one, DOX molecules stacked up instead of being randomly distributed.
Another advantage of this re-engjneered polymer was that it was pH-sensitive. DOX release from the modified polymer accelerated in acidic environments, but slowed In a pH similar to that of blood. This means that less DOX would be released into blood, white concurrently a pH trigger could potentially be applied to spur more aggressive release of DOX at the site itself.
While the research is far from the stage of clinical trials, the team's work builds a foundation for engineering more effective DOX corners and holds much potential in achieving a controlled release of DOX.