Hyaluronic Acid?Dexamethasone Nanoparticles for Local Adjunct Therapy of Lung Inflammation

CANDELARIA INÉS CÁMARA; LAURA BERTOCCHI; CATERINA RICCI; ROSARIA BASSI; ANNALISA BIANCHERA; LAURA F. CANTÚ; RUGGERO BETTINI; ELENA DEL FAVERO

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Lugar: Basel; Año: 2021 vol. 22 p. 1 - 18

1422-0067

The delivery of a dexamethasone formulation directly into the lung appears as an appropriate strategy to strengthen the systemic administration, reducing the dosage in the treatment oflung severe inflammations. For this purpose, a hyaluronic acid-dexamethasone formulation wasdeveloped, affording an inhalable reconstituted nanosuspension suitable to be aerosolized. Thephysico-chemical and biopharmaceutical properties of the formulation were tested: size, stability,loading of the spray-dried dry powder, reconstitution capability upon redispersion in aqueous media.Detailed structural insights on nanoparticles after reconstitution were obtained by light and X-rayscattering techniques. (1) The size of the nanoparticles, around 200 nm, is in the proper range for apossible engulfment by macrophages. (2) Their structure is of the core-shell type, hosting dexamethasone nanocrystals inside and carrying hyaluronic acid chains on the surface. This specific structureallows for nanosuspension stability and provides nanoparticles with muco-inert properties. (3) Thenanosuspension can be efficiently aerosolized, allowing for a high drug fraction potentially reachingthe deep lung. Thus, this formulation represents a promising tool for the lung administration vianebulization directly in the pipe of ventilators, to be used as such or as adjunct therapy for severelung inflammation.