Locust bean gum microparticles as carriers for lung delivery of bacterial lysates
Joana Pinto-da-Silva1#, Joana Cruz1,2# & Ana Grenha1,2
1Centre for Marine Sciences, Universidade do Algarve, Campus de Gambelas, Faro, 8005-139, Portugal
2Faculdade de Ciências e Tecnologia, Universidade do Algarve, Campus Gambelas, Faro, 8005-139, Portugal #equally contributing authors
Bacterial lysates (BL) are used as immunomodulators to prevent respiratory infections, being typically administered orally, which limits their potential to generate strong mucosal immunity in the lung. This work consists in repurposing bacterial lysates for immunisation against respiratory infections, proposing immunisation via inhalation to mitigate efficacy issues associated with conventional oral delivery. The main aim is to reach the mid-lung region and the smaller airways and generate a local immune response, along with a systemic effect. Used as model, a commercial formulation of BL was converted into inhalable microparticles (MP) by spray-drying, associating locust bean gum (LBG). LBG is a galactomannan which mannose units are expected to mediate specific targeting of lung resident antigen presenting cells through interaction with mannose surface receptors. BL-loaded MP were successfully produced with varied LBG/BL mass ratios and the effective association of BL was confirmed. Aerodynamic evaluation of the MP revealed mass median aerodynamic diameters (MMAD) with potential to reach the lung (< 5 µm) for optimised formulations. An evaluation of the effect of MP in alveolar epithelial (A549) cells suggested dose-dependent toxicity, which requires attention. Overall, the data obtained so far are encouraging for pursuing the evaluation of LBG MP as carriers of bacterial lysates to the lung aimed at the prevention of respiratory diseases.
Aerodynamically suitable microparticles containing bacterial lysates can be obtained by spray-drying, supporting an application as inhalable platform for immunisation against respiratory infections.