Respiratory inflammation diseases such as asthma, Cystic Fibrosis (CF), emphysema and Chronic Obstructive Pulmonary Disease (COPD) are a major world health problem in the 21st century. Current therapies in use do not address the underlying inflammation pathway and new interventions are urgently needed to address this unmet clinical need. Currently employed medications include both short and long-acting bronchodilators such as Salbutamol and Tiotropium (Spiriva) working as either β2-agonists or muscarinic agonists. As an approach to improve quality of life and lung function, further β2-agonists are used in combination therapy with Corticosteroids such as Budesonide. However, there are side-effects to these combination therapies including upper respiratory infection and increased risk of pneumonia, furthermore they have not been shown to reduce hospital admissions or risk of mortality.
Prevention or minimisation of the inflammation pathway in diseased lungs offers the best method of slowing the progression of disease. The development of RNA interference, in particular small interfering RNA (siRNA), allows silencing of genes coding for inflammatory cytokines (e.g. IL-8) to be targeted with potency and accuracy.
While the potential of siRNA has been recognised, effective delivery has been a major factor limiting their clinical success to-date. We have developed an inhalable platform based on regulatory approved excipient, Polylactide-co-glycolic acid (PLGA), which can be engineered into nanoparticles to target siRNA to airway epithelial cells. Herein, we propose optmisation and integration of these siRNA therapeutic nanoparticles with state-of-the-art respiratory delivery devices which will aid in progression towards future animal studies and Phase I clinical trial.
