PhD defence I.(Imco) Sibum

Resistance is futile. The targeted delivery of antibiotics to the lung.

Tuberculosis (TB) is an infectious disease that causes 1.5 million deaths annually. Treatment of TB is becoming more difficult due to the increasing incidence of resistant pathogens. In some countries half of the patients are resistant against the two first-line antibiotics isoniazid and rifampicin. Resistance may be overcome by increasing the amount of antibiotic at the site of infection, but the dose that can be administered orally or via infusion is limited by the severity of the side effects. Increasing the dose may increase these to an intolerable level. Alternatively, antibiotics could be delivered locally. Targeting results in a higher amount of drug at the site of infection while reducing side effects. Because TB is predominantly a lung disease the administration of antibiotics via inhalation seems rational.

At present, the administration of medicines via inhalation is mainly used for low-dose medicines (< 2.5 milligrams), but antibiotics are high-dose medicines, up to three hundred milligrams. New techniques are necessary to enable administration of high-dose drugs by inhalation. For example, there is no space for the excipients used in low-dose drugs. In his thesis Imco Sibum has described the different aspects for the administration of high-dose drugs via inhalation. Extensive research has been done into the development of an inhaler for isoniazid, which was a challenge due to particle growth. Finally, it was investigated whether isoniazid, and the antibiotic amikacin, could be automatically filled into inhalers. This allowed for higher doses. The results of this research are a good starting point for the clinical development of new treatment options for the treatment of TB.

Promotor: Prof.dr. H.W. Frijlink

Co-supervisor: dr. F. Grasmeijer