Inhalable Spray-Dried Carriers for Deep Lung Delivery and In Situ Synthesis of Allicin

Allicin exhibits several therapeutic properties, but its clinical use is limited by its high instability and low bioavailability. Furthermore, although pulmonary delivery of allicin offers a promising approach for treating various respiratory diseases, direct exposure of the lungs to allicin through aerosols or vapors carries a significant risk of respiratory tract irritation or tissue damage. Facing these challenges, we propose a novel bioinspired strategy that facilitates the in situ synthesis of allicin from its stabilized precursors using the Büchi Mini Spray Dryer equipped with a three-fluid (3F) nozzle to develop inhalable carriers suitable for deep lung delivery. We have identified conditions that ensure successful coencapsulation of both enzyme and substrate within maltodextrin core-shell microparticles, and we have examined the effects of selected additives on allicin yield and aerosolization performance under various storage conditions. Each 3F particle acts as an independent enzyme-substrate system that, upon deposition, dissolves and releases active allicin within the network of the respiratory tract. We believe that such microcarriers may help overcome the challenges of pulmonary delivery of allicin and other unstable compounds.