Drug delivery: A tiny timely vehicle
9/5/2005 London, England Jenny Bangham [email protected] The administration of chemotherapy together with anti-angiogenic drugs seems to be a particularly effective way of slowing tumour growth. However, this combination also poses some practical problems — cutting off the tumour blood supply makes it difficult to achieve a high drug concentration, and hypoxia can trigger the expression of chemotherapy-resistance genes. Now, a group led by Ram Sasisekharan has designed a sophisticated delivery system that gets around these complications — a 'nanocell' that localizes to tumours and then shuts down the tumour vasculature before delivering a cytotoxic agent to tumour cells. Their nanocell consists of a phosopholipid envelope and, inside it, a nanoparticle made of a biodegradable polymer. The researchers incorporated an anti-angiogenic agent — in this case combretastatin — into the liposome, and attached the chemotherapeutic agent doxorubicin to the nanoparticle. They found that combretastatin escapes rapidly from the lipid envelope, while the conjugated doxorubicin is freed more slowly, degrading into smaller, inactive fragments before breaking down further into free, active doxorubicin. These release kinetics correlate well with the effect of the nanocell combination on the tumour endothelium in vitro — the system caused the vasculature to collapse as early as 12 hours post-administration, and tumours to be completely ablated by 30 hours. The authors tested the therapeutic efficacy of this system in vivo using mice with B16:F10 melanomas and mice with Lewis lung carcinoma. They compared the effects of sequential drug delivery using nanocells with several other treatments —one or both [...]