For many years, respiratory diseases have been treated with drugs delivered via inhalers.
Sufferers from asthma and chronic obstructive pulmonary disease (COPD) are extremely familiar with the technique but research is now advanced on using the same pathway as a route for delivering drugs for the treatment of a wider range of conditions. Cystic fibrosis, neurological conditions, bacterial infections and even cancers have been mooted as possible targets, as well as pain management and vaccines. Additionally, existing drugs delivered in this way could have different effects from those they demonstrate when administered by other routes. For example, the anti-depressant amitriptyline, by blocking ceramide levels, has the potential to treat inflammation and infections in the respiratory tract. Using the lungs as a delivery pathway has both advantages and challenges. On the negative side, the lungs are powerfully resistant to allowing molecules to cross into the bloodstream as a necessary immune response but, conversely, they provide a large area for absorption with easy access to the blood supply.
If drugs can be made to enter the body via this route, it can reduce the size of the dose necessary. Lower doses have the benefit of reducing the incidence of side effects, a positive result for both patients and drug developers. Administration via an inhaler rather than orally can also mean drugs act faster on the system, making it an attractive proposition where a rapid effect is desired, for example in pain relief or easing a craving for cigarettes. In cystic fibrosis and bronchiectasis, resistance to antibiotics is becoming a problem for treatment of infections but a €50 million Europe-wide research project is being led by Queen’s University, Belfast, to produce inhaled antibiotics which are more effective. The university said that the iABC (inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis) consortium will develop new inhaled antibiotics to manage chronic lung infection, the main cause of disease and death in patients with cystic fibrosis and bronchiectasis. The new antibiotics are to be trialled over a five year period and are expected to improve patients’ quality of life by reducing lung infections and flare ups, improving lung function and overcoming antibacterial resistance which frequently occurs in patients with these conditions.
Professor Stuart Elborn, Dean of the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University, and lead researcher on the project, said: “There are limited antibiotics available to treat lung infection in cystic fibrosis and bronchiectasis, and the bacteria causing them are becoming increasingly resistant to current antibiotics. In addition, work is under way to treat diabetes with inhalers, seen by some as particularly useful for sufferers who find injecting themselves stressful. Inhaled insulin has gone on sale in the US this year for patients with both type 1 and type 2 diabetes. Because inhalation drug development is mostly not about new compounds rather new delivery options it is known as repositioning and presents many engineering problems which must be overcome to devise workable inhalers which deliver the correct dose to the correct portion of the respiratory system in a reliable way which is acceptable to patients and easy for them to use.
Engineers are working on everything from the type of plastic used to the speed of delivery. Four types of system are widely used; metered dose inhalers (MDI), dry powder inhalers (DPI), liquid droplet inhalers (LDI) and nebulisers. MDIs are the market leaders with almost half of sales but DPIs are growing in popularity, partly because they do not rely on a propellant to deliver the dose. Conferences and symposia are being held around the world every few months to keep people abreast of this exciting and rapidly developing field. Patients with all kinds of conditions will increasingly be growing used to inhaling their medicine where in the past pills or injections were the norm.
“This work has the potential to deliver inhaled antibiotics that will improve the quality of life and survival of cystic fibrosis and bronchiectasis patients.”
Professor Stuart Elborn
Dean of the School of Medicine, Dentistry and Biomedical Sciences at Queen’s University