Losartan-chitosan/dextran sulfate microplex as a carrier to lung therapeutics: Dry powder inhalation, aerodynamic profile and pulmonary tolerability

Abstract

This study aims to obtain an inhalation powder with meaningful aerodynamic and safety profiles for the lung delivery of losartan (LS). For this, the capacity of self-assembly of chitosan (CS) and dextran sulfate (DS) to form CS/DS microplex (MC), incorporating high payload of hydrophilic LS was harnessed. Dry powder inhaler (LS-MC-DPI), prepared via spray drying of the best achieved LS-MC, was proposed to impart precise engineered inhalation characteristics. Micrometric robust CS/DS MC was revealed to offer the opportunity to heighten LS encapsulation, accounting for ~75%. LS-MC-DPI was successfully developed with high yield, flowability, respirable aerodynamic size and morphology which formed swellable and mucoadhesive network, facilitating intra-pulmonary delivery. Moreover, sustained release pattern, augmented deep lung deposition and safe histological profile were realized. Overall, the newly developed LS-MC DPI shows promises as an inhalation system. The aerodynamic performance and safety of LS-MC-DPI verify its suitability for further in vivo lung therapeutics.

Keywords: Chitosan; Dextran sulfate; Dry powder inhaler; Losartan; Microplex; Pulmonary tolerability.