Development of a New Treatment Modality for Lung Diseases That Uses Innovative Fine Droplet Drying (fdd) Technology Offering Inhalable Nano/microparticles-incorporated Therapeutic Agents

Abstract

Dr Takashi Sato is a researcher at the Department of Pulmonology, Yokohama City University in Japan. He is working in conjunction with collaborators, Dr Shimosato from Shinshu University, Japan and Dr Klinman from the National Cancer Institute of the National Institutes of Health (NIH), to develop and improve technologies for the delivery of cost-effective inhalational therapies for pulmonary diseases. Their current focus is on therapy that can thwart lung cancer. Sato and his colleagues developed their broad understanding of pulmonology over many years of research and study. They use their creativity and knowledge of the field to develop novel treatment options for lung disease. Sato became interested in this therapeutic strategy while studying how oxidative stress (the strain put on the body from inhaling certain harmful chemicals) supported the development of silicosis, a lung disease caused by inhaling silica particles. When training with Klinman, Sato developed the idea of using particles of similar size (but without pathogenic particles) to treat rather than cause pulmonary disease. He recognised that inhalational therapy might be used to treat both pulmonary and non-pulmonary diseases. This marked the beginnings of his effort to develop inhalable nano/microparticles containing immunomodulatory oligodeoxynucleotides. He postulated that these could be harnessed to treat a variety of immune-mediated diseases as well as diseases that would benefit from enhanced immunity (such as cancer). "Findings from this work would contribute to the real-world health care with less needles; just inhale deeply, even in the lethal malignant diseases like lung cancer," Sato says. In the past ten years, Sato focused his research efforts on improving and broadening the scope of inhalation therapies. He synthesised biodegradable polymer nanoparticles carrying oligodeoxynucleotides that could be used for immunotherapy. "I also established that the effect of these particles could be readily monitored in murine models, showing that the nanoparticles reached inflammatory lesions in the lungs and caused them to regress when delivered by intratracheal instillation," explains Sato. Published studies by Sato, Shimosato and Klinman document the promise of this strategy. One of their projects began with 'Nintedanib (OFEV' Boehringer Ingelheim GmbH)', a medicine in pill form used to treat Idiopathic Pulmonary Fibrosis, a disease which causes scarring to the lungs. The team was able to create a particle form of the medication suitable for inhalation treatment. Based on the favourable preclinical results, they are moving forward towards human trials. While effect for delivery of immunostimulatory oligos to the lungs, inhalational therapy is not optimal for their delivery elsewhere in the body. Dr Sato's team is therefore interested in developing nano/microparticles that can deliver these oligodeoxynucleotides orally. While uptake through the gastrointestinal tract has been achieved, dosage remains a problem. Thus, this approach remains potentially useful for the delivery of oligos to cells lining the gastrointestinal tract but remains problematic for systemic therapy.