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Posted: December 16, 2008
Advance in Dendrimer-Based Drug-Delivery Program Reduces Toxicity of Cancer Drug
(Nanowerk News) Starpharma Holdings Ltd today reported an important advance in its dendrimer-based drug-delivery program.
A Starpharma dendrimer combined with a widely-used cancer drug (doxorubicin) has achieved a significant extension of the drug's plasma half-life and a marked reduction in drug toxicity compared to administration of the drug alone. In this proof-of-concept animal study the efficacy of the dendrimer-drug construct was equivalent to that of the drug alone.
Doxorubicin was selected to illustrate the delivery technique because of its wide use as an anticancer agent, having application in Hodgkin's lymphoma, some leukemias, as well as cancers of the breast, lung, and ovaries. The clinical use of doxorubicin is often constrained by its cardiac toxicity which may result in congestive heart failure and dilated cardiomyopathy.
In Starpharma's recent study, an animal cancer-model ("xenograft") showed that Starpharma's dendrimer-doxorubicin construct (SPL8181) achieved the same inhibition of human breast-cancer tissue as doxorubicin alone, but with markedly reduced cardiac toxicity. Blinded histopathological examination of cardiac tissue samples from the dosed animals revealed significantly lower cardiotoxicity (p=0.019) in the dendrimer-doxorubicin construct treatment group (toxicity in 14% of samples) compared to a doxorubicin-only treatment group (toxicity in 86% of samples). Signs of reduced toxicity in other organs were also observed for the animals dosed with the dendrimer-based molecule compared to doxorubicin alone.
Starpharma's delivery technology works by attaching multiple drug molecules to the surface of a dendrimer nanoparticle. The result is that the dendrimer nanoparticle can target the drug to the tumour, in preference to other organs. Additionally Starpharma's proprietary dendrimer technology has been engineered to allow for the drug payload to be preferentially released from the nanoparticle in close proximity to the tumour.
Starpharma CEO, Dr Jackie Fairley said "Starpharma has already formed a number of partnerships based on its drug-delivery technology, including a dermal program with Stiefel Laboratories. The technology has application for both small molecule drugs and protein therapeutics and Starpharma is in advanced discussions with additional potential partners who have an interest in using it to improve the delivery, efficacy, and toxicity profile of their products."
The animal studies were conducted in collaboration with Associate Professor Chris Porter of the Victorian College of Pharmacy and Dr Carleen Cullinane of the Peter MacCallum Cancer Centre.
Starpharma has already taken a dendrimer-based drug into clinical trials conducted to US FDA requirements: VivaGel(R) vaginal microbicide is currently in Phase II clinical trials, and is the subject of a license agreement with Durex(R) condoms for use as a condom coating.