Engineered sodium hyaluronate respirable dry powders for pulmonary drug delivery

Francesco Martinelli, Anna Giulia Balducci, Abhinav Kumar, Fabio Sonvico, Ben Forbes, Ruggero Bettini, Francesca Buttini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)
461 Downloads (Pure)

Abstract

Sodium hyaluronate (HYA) warrants attention as a material for inhalation due to its (i) therapeutic potential, (ii) utility as a formulation excipient or drug carrier, and (iii) ability to target lung inflammation and cancer. This study aimed to overcome formulation and manufacturing impediments to engineer biocompatible spray-dried HYA powders for inhalation. Novel methodology was developed to produce HYA microparticles by spray drying. Different types of surfactant were included in the formulation to improve powder respirability, which was evaluated in vitro using cascade impactors. The individual formulation components and formulated products were evaluated for their biocompatibility with A549 respiratory epithelial cells. The inclusion of stearyl surfactants, 5% w/v, produced the most respirable HYA-powders; FPF 59.0–66.3%. A trend to marginally higher respirability was observed for powders containing stearylamine > stearyl alcohol > cetostearyl alcohol. Pure HYA was biocompatible with A549 cells at all concentrations measured, but the biocompatibility of the stearyl surfactants (based on lethal concentration 50%; LC50) in the MTT assay ranked stearyl alcohol > cetostearyl alcohol > stearylamine with LC50 of 24.7, 13.2 and 1.8 μg/mL, respectively. We report the first respirable HYA powders produced by spray-drying. A lead formulation containing 5% stearyl alcohol was identified for further studies aimed at translating the proposed benefits of inhaled HYA into safe and clinically effective HYA products.

Original languageEnglish
Pages (from-to)286-295
Number of pages10
JournalINTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume517
Issue number1-2
Early online date5 Dec 2016
DOIs
Publication statusPublished - 30 Jan 2017

Keywords

  • Hyaluronic acid
  • hyaluronan
  • inhalation toxicology
  • dry powder inhaler
  • particle engineering

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