Indacaterol/Ciclesonide Delivery: A Promising Strategy to Improve Pharmacodynamic Outcomes in Asthma models

Background: Asthma is a chronic inflammatory disease of the respiratory system for which there is currently no cure. The available treatments can only control and decrease the symptoms and exacerbations. Combined steroid and bronchodilator therapies are considered the first-line approach to asthma management and are preferably administered via inhalation to limit systemic side effects and reduce the required doses. Nonetheless, most currently available formulations exhibit low pulmonary deposition of active compounds. Combined with rapid mucociliary clearance and macrophage-mediated elimination, low bioavailability, and high systemic absorption, this often necessitates frequent administration and higher doses. In addition, effective asthma management relies on regular and consistent use of inhaled therapies to maintain disease control. This often results in suboptimal patient adherence to prescribed regimens, highlighting the need for simplified treatment strategies. Purpose: Our aim is to address some of the challenges in asthma management by producing an innovative formulation containing Indacaterol/Ciclesonide (IND/CIC), which will be converted into a dry powder for inhalation. Methods: We first evaluated the efficacy and pharmacological potency of IND/CIC formulations with an ex vivo model of methacholine’s pre-contracted rat tracheal rings using an organ bath system. Subsequently, we used an acute ovalbumin (OVA)-induced mouse model of eosinophilic asthma. Balb/C mice received 10 µg OVA via intraperitoneal injection on days 1 and 8 and were challenged with OVA’s aerosol on days 24-25-26. Mice were treated from day 21 to day 26 with IND/CIC formulations, and sacrificed on day 27. Lung tissue, plasma, and broncho-alveolar lavage fluid (BALF) were collected to assess the anti-inflammatory activity of CIC, while IND’s bronchodilatory efficacy was evaluated by measuring lung mechanics parameters using the FlexiVent® system.