Respiratory inflammation is an umbrella term which encompasses numerous disease states such as asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Current approaches to therapy mainly involve the use of inhalers containing either short acting (Salbutamol) or long acting (Tiotropium) bronchodilators or a combination of both. While effective in the initial instances these therapies are often subject to failed usage techniques or poor patient adherence thus allowing the inflammation to recur. Furthermore, these therapies are plagued by numerous side effects such as an increased risk of both oral and respiratory infections. The concept of RNA interference (RNAi) represents a viable alternative in the treatment of respiratory inflammatory conditions as it reduces the inflammation itself rather than simply opening the airways via direct stimulation. Small interfering RNA (siRNA) is the cornerstone of RNAi. siRNA allows for the targeted “silencing” of a particular gene of interest i.e. genes resulting in the inflammatory state within the respiratory tract such as IL-8. siRNA is highly specific, potent and associated with a side effect free profile. The effective delivery of siRNA to the region of interest within the body represents the main rate limiting step in harnessing the potent therapeutic potential of RNAi. Herein we propose optimisation of the formulation of these siRNA-PLL polyplexes as well as testing on a cell line representative of the respiratory tract to aid in the progression towards future animal studies.
