Abstract Rationale Available inhalation therapy for asthma is dedicated to control symptoms and prevent exacerbations. Combined corticosteroid and bronchodilator therapies remain the cornerstone of asthma management and are preferably administered via inhalation to limit doses and systemic exposure. Nonetheless, current inhalable formulations present several drawbacks, including poor pulmonary deposition, rapid mucociliary clearance, macrophage-mediated elimination, and substantial systemic absorption. These factors limit pulmonary drug availability, necessitating higher doses and more frequent administrations. In addition, effective asthma management depends on consistent patient adherence to inhaled therapies, which is often suboptimal, underscoring the need for simplified treatment strategies. This study aims to develop an innovative formulation containing Indacaterol/Ciclesonide (IND/CIC)-loaded liposomes, which will be subsequently engineered into a dry powder for inhalation. The goal is to enhance pulmonary retention of both drugs, thereby reducing required doses, posology, and side effects. This will be achieved by leveraging the targeted, local and sustained drug release provided by the liposomes, and by optimizing pulmonary deposition of the final dry powder using innovative excipients such as hydroxypropyl-beta-cyclodextrins (HP-β-CD). Methods Pharmacological potency of IND/CIC-loaded liposomes was first evaluated ex vivo using methacholine-precontracted rat tracheal rings. Subsequently, their therapeutic potential was evaluated in an ovalbumin (OVA)-induced eosinophilic asthma mouse model. Balb/C mice were sensitized with OVA intraperitoneally (days 1 and 8) and challenged via aerosol (days 24-25-26). Treatments with liposomal or free IND/CIC were administered from days 21–27 at low (IND: 12.3 µg/mL, CIC: 13.04 µg/mL) and high (IND: 123.0 µg/mL, CIC: 130.4 µg/mL) concentrations. Lung tissue, plasma, and bronchoalveolar lavage fluid (BALF) were collected, and lung mechanics were assessed with the FlexiVent system. Results Ex vivo , liposomal IND/CIC produced stronger tracheal smooth muscles relaxation as compared to non-liposomal IND, reflected by a lower EC50. In vivo, both liposomal concentrations significantly reduced airway resistance and elastance while increasing compliance and inspiratory capacity compared to free-drug solutions. Moreover, IND/CIC liposomal treatments substantially decreased BALF eosinophils, peribronchial inflammation and IL-4, IL-5, IL-13, IL-33, and TSLP levels relative to matched free-drug solutions. Interestingly, low-concentration liposomes achieved superior bronchodilatory and anti-inflammatory efficacy compared to the high-concentration liposomal formulation. Conclusion Liposomal encapsulation of IND/CIC enhances bronchodilatory and anti-inflammatory efficacy compared with free-drug formulations while exhibiting a clear dose-sparing effect. These findings highlight the potential of liposomal inhalable formulations to optimize corticosteroid–bronchodilator combination therapy, offering a more effective approach to asthma management. This abstract is funded by: Wallon region, Aquilon pharma
Bottero et al. (Fri,) studied this question.