The efficiency of Herceptin in treating tumours affecting the brain or central nervous system is believed to have been limited by the blood-brain tumour barrier (BTB). Now researchers believe that the class of drugs used to treat erectile dysfunction could help overcome the BTB.
In a paper published online last month in PLoS One researchers detail an investigation into the impact Levitra, an erectile dysfunction drug, has on Herceptin delivery to brain metastases of lung and breast cancers.
Combining oral administration of Levitra and intravenous delivery of Herceptin increased survival time by 20 to 30 per cent in two of the three tumour types investigated compared to Herceptin alone. Furthermore, treatment with Levitra and Herceptin increased tumour apoptosis.
These results were achieved without Herceptin accumulating in healthy tissue because Levitra increased Herceptin delivery through the BTB but not the blood-brain barrier (BBB), according to the researchers.
Increasing BTB permeability
Levitra, and other erectile dysfunction treatments such as Pfizer’s Viagra (sildenafil), work by inhibiting phosphodiesterase type 5 (PDE5). Modulating PDE5 leads to intracellular accumulation of cyclic guanosine monophosphate (cGMP) which may increase permeability of capillaries.
By increasing the permeability of capillaries this class of drugs can treat erectile dysfunction but researchers are now also looking at the potential to affect microvessels in brain tumours.
This research suggests that PDE5 inhibitors increase BTB permeability to high molecular weight drugs, creating the possibility they could be used to improve delivery of a range of therapeutics including nanomedicines.