Hyaluronic acid-based nanoparticles for pulmonary delivery of poorly soluble drugs

The delivery of poorly soluble drugs poses significant challenges in pharmacotherapy, particularly for corticosteroids. This study investigates the development of hyaluronic acid-based nanoparticles to enhance the solubility and bioavailability of dexamethasone. Hyaluronic acid-dexamethasone formulations, (HAm 15–30 kDa and HAl 750–1000 kDa), were produced as stable powders to be resuspended. We characterized the nanoparticles formed after resuspension by laser-light and X-ray scattering. Nanoparticles showed nanometric size, good stability, a core-shell arrangement, and muco-inert properties. We evaluated the interaction of nanoparticles with lung surfactant models, by nebulization of formulations on DPPC Langmuir monolayers to mimic their effects on alveolar interfaces when administered via nebulization. They showed good biocompatibility and enhanced anti-inflammatory response, as assessed by pro-inflammatory cytokine TNF-α release in LPS-stimulated macrophages. The favorable structural and biopharmaceutical characteristics of HA-based formulations can be exploited to improve the delivery of poorly soluble drugs to the lungs by inhalation. • Two hyaluronic acid–dexamethasone (HA–Dex) formulations were obtained using HA of different MW, modulating size and surface of nanoparticles'. • Both nanosystems remained stable and structurally intact in the presence of mucin, showing limited mucoadhesion and good dispersion behavior. • The HA–Dex nanodispersions were suitable for nebulization, and interacted with pulmonary surfactant models. • These findings highlight the suitability of HA–Dex nanoparticles as promising carriers for inhaled corticosteroid delivery.