In-flight electro-neutralisation electrospray for pulmonary drug delivery

Abstract

Pulmonary drug delivery does not only provide non-invasive therapy for local lung diseases but also remarkably enhances systemic absorption of therapeutics owing to the tremendous surface area of the lung and fast transport of active molecules across the respiratory epithelia. In comparison to traditional delivery systems, electrohydrodynamic atomisation (EHDA) is superior in terms of size and production rate control but the high surface charges of resulting particles prohibit its use in drug delivery. To overcome this challenge, we developed an in-flight electro-neutralisation electrospray (IFENE) method which enables the generation of mists of particles in respirable size range with little to no charge. Our approach uses low-frequency alternating current (AC) to produce charge-neutralised sprays with initial velocity due to oppositely charged droplets combination. Experiments and simulations with pure liquid as the working solution were conducted to reveal the underlying mechanism. The applied frequency is found to be the main factor that influences spray stability and formation. Poly (vinylidene fluoride) (PVDF) and PVDF with curcumin solution were electrosprayed via IFENE, producing sprays of organic particles with controlled sizes and neutralised charges. The capability of coupling particle generation in the respirable size range (below 5 μm) and charge reduction (under 400 femtoamperes), along with its simple setup makes IFENE a promising platform technology in inhalation drug delivery.