Respiratory delivery moves beyond the lung

Success in treating respiratory diseases with inhaled formulations inspired research into expanding respiratory delivery to treat systemic diseases. "All the scientific evidence to date indicates that the systemic bioavailability via the respiratory route is vastly higher than noninvasive or nondisruptive percutaneous absorption," according to Igor Gonda, CEO of Aradigm (Hayward, CA).

Simes agrees. "If the drug is safe and can escape the lungs' natural clearance mechanisms until their therapeutic payload has been delivered, it can achieve equivalent or higher bioavailability than pecutaneous injection." Respiratory delivery is "particularly useful for the delivery of drugs to distant target organs through the circulatory system," Simes adds.

Future inhalable treatments

As companies continue their pursuit of inhalable treatments for diabetes and respiratory diseases, researchers investigate other diseases that could potentially be managed through respiratory drug delivery. BioSante believes drugs that could be delivered through the lungs include the protein human Factor IX for hemophilia and Interferon alpha-2b for chronic hepatitis B.

A 2007 study shows that inhaled drug delivery can effectively combat measles, Sievers says. Dilraj and his colleagues demonstrated that children revaccinated with Edmonston–Zagreb wet-mist aerosol had a stronger and longer-lasting antibody response six years later than those revaccinated subcutaneously (2). Wet-aerosol vaccination, Sievers observes, could thus provide durable protection against this disease.

The World Health Organization and the Serum Institute of India are directing Phase I clinical studies with a wet-mist aerosol measles vaccine in India.

Sievers adds that DelSite (Irving, TX) recently developed a flu vaccine in gel form for intranasal delivery. "If you ship a powder around the world and store it, you have to ship high-purity water for injection along to reconstitute it," he explains. Although powders and liquid suspensions are susceptible to contamination and decomposition, dry powders are generally more stable than liquid suspensions. DelSite's formulation is "easier to store and less susceptible to bacterial contamination than a liquid suspension would be," he says.

Conclusion

Despite the problems that Exubera and AERx encountered, scientists and pharmaceutical companies confirm that the respiratory delivery of insulin and other biologicals remains a practical and worthy goal. Dalby agrees but cautions that some obstacles remain. Bringing new inhaled therapies to market requires the "re-emergence of financiers, bitten once by problems with insulin," who are undaunted by long development cycles and regulatory uncertainties, he says. The market must also be "willing and able to pay for the eventual product," Dalby adds.

Sievers is optimistic about the prospects for future inhaled therapies. When doctors do not have "an existing, well established protocol and treatment" for a disease, he says, an inhaled formulation will be successful. "Pick a new drug or pick a disease that we haven't licked yet, and you've got a winner," he concludes.

References

1. B. Frederiksen et al., "Effect of Aerosolized rhDNase (Pulmozyme) on Pulmonary Colonization in Patients with Cystic Fibrosis," Acta Paed. 95 (9), 1070–1074 (2006).

2.A. Dilraj et al., "Aerosol and Subcutaneous Measles Vaccine: Measles Antibody Responses 6 Years After Re-Vaccination," Vaccine 25 (21), 4170–4174 (2007).

For more on this topic, see the online exclusive "Journey to the Center of the Lung"