Dry powder of budesonide/hydroxypropyl-beta-cyclodextrin complex for inhalation as a new potential antiasthmatic treatment

Asthma is a respiratory disease characterized by chronic airway inflammation which can lead, if not correctly managed, to tissue remodeling associated with an irreversible decline in lung function. Hypersensitivity of the respiratory tract to non-specific stimuli, which causes triggering of asthma attacks, is also observed. Despite medical advances, asthma remains an important socio-economic and public health concern since this condition affects 300 million people and causes more than 300 000 deaths worldwide every year. Furthermore its annual cost is estimated at over 30 billion euros in Europe. These issues can be partially linked to an inadequate control of asthma due to undesirable effects of existing medication such as corticosteroids. Hence, the development of new medications with improved effectiveness and reduced adverse effects could allow a better management of the disease. It has been recently discovered that inhaled solution of hydroxylpropyl-beta-cyclodextrin (HPBCD) is able to reduce allergen-induced bronchoconstriction in asthmatic patients, with no toxicity observed in healthy patients further to administration. Based on these results, our project seeks to develop new antiasthmatic medication containing an association of HPBCD and budesonide, a widely used corticosteroid in long-term treatment of asthma. Thus, we investigated complexation between the two molecules. Interestingly, it was observed that when budesonide is complexed with HPBCD, its permeability across a Calu-3 cell layer is reduced. Several experiments in mouse models confirmed that HPBCD acts as a sustained delivery system which progressively releases budesonide into the lung parenchyma, leading to a prolonged anti-inflammatory effect. Due to high Peclet number of HPBCD, the spray dried complex exhibited wrinkled particles whose interest in dry powder for inhalation is well known. Thanks to its anti-inflammatory effect and its sustained release potential, HPBCD could significantly reduce corticosteroids needed doses for management of asthma. However, a clinical study has to be performed to determine the optimal budesonide/HPBCD ratio and the minimal effective dose of complex. Further investigations are also needed to exploit the potential of spray dried HPBCD and develop a powder for inhalation by particle engineering.