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

Int J Mol Sci. 2021 Sep 28;22(19):10480. doi: 10.3390/ijms221910480.

Abstract

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 of lung severe inflammations. For this purpose, a hyaluronic acid-dexamethasone formulation was developed, affording an inhalable reconstituted nanosuspension suitable to be aerosolized. The physico-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-ray scattering techniques. (1) The size of the nanoparticles, around 200 nm, is in the proper range for a possible 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 structure allows for nanosuspension stability and provides nanoparticles with muco-inert properties. (3) The nanosuspension can be efficiently aerosolized, allowing for a high drug fraction potentially reaching the deep lung. Thus, this formulation represents a promising tool for the lung administration via nebulization directly in the pipe of ventilators, to be used as such or as adjunct therapy for severe lung inflammation.

Keywords: X-ray scattering; drug delivery; light scattering; lung administration; mucus interaction; nanocrystals; nanoparticle characterization.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Dexamethasone / chemistry*
  • Dexamethasone / pharmacology
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hyaluronic Acid / pharmacology
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Pneumonia / drug therapy*

Substances

  • Aerosols
  • Dexamethasone
  • Hyaluronic Acid