New research presented at this week's British Pharmaceutical Conference has suggested that it may be possible to deliver DNA to the lung using a simple pressurised metered dose inhaler (pMDI). The finding could open up new avenues for the treatment of diseases such as cystic fibrosis and alpha-1 antitrypsin deficiency.
Gene therapy approaches to diseases such as CF have been held back by the need to use viral vectors to deliver the therapeutic DNA molecules. In fact, initial progress in the field was dealt a bitter blow in 1999 when a patient died after receiving a treatment for a rare genetic liver disease based on an adenoviral vector. Thereafter, clampdowns on the conduct of gene therapy trials were implemented in many countries around the world, holding back clinical research in this area.
This forced scientists to look at non-viral vectors for DNA delivery, and one interesting approach is the use of complexes based on plasmid DNA and cationic lipids, known as lipoplexes.
"At present, nebulisation is used to aerosolise lipoplex solutions to the lung," said the researchers, from King's College London, UK. "However, nebulisation is inefficient and pMDIs, which are commonly used for the treatment of asthma, would be better devices for targeting DNA to the lung."
The scientists describe a technique for combining a model DNA sequence with the cationic lipids, propellant (HFA), surfactant and other factors required for successful delivery using a pMDI. The functionality of the approach, i.e. its ability to deliver genetic material effectively to the lung, is still under investigation.
One issue which must still be resolved is whether the formulation will impact on the integrity of the DNA; for example, the researchers note that the use of surfactant may alter the solubility of the lipid:DNA complex.