Quantitative assessment of nanoparticle surface hydrophobicity and its influence on pulmonary biocompatibility

Marie-Christine Jones, Stuart A Jones, Yanira Riffo-Vasquez, Domenico Spina, Ewelina Hoffman, Anna Morgan, Aateka Patel, Clive Page, Ben Forbes, Lea Ann Dailey

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


To date, the role of nanoparticle surface hydrophobicity has not been investigated quantitatively in relation to pulmonary biocompatibility. A panel of nanoparticles spanning three different biomaterial types, pegylated lipid nanocapsules, polyvinyl acetate (PVAc) and polystyrene nanoparticles, were characterized for size, surface charge, and stability in biofluids. Surface hydrophobicity of five nanoparticles (50-150nm) was quantified using hydrophobic interaction chromatography (HIC) and classified using a purpose-developed hydrophobicity scale: the HIC index, range from 0.00 (hydrophilic) to 1.00 (hydrophobic). This enabled the relationship between the nanomaterial HIC index value and acute lung inflammation after pulmonary administration to mice to be investigated. The nanomaterials with low HIC index values (between 0.50 and 0.64) elicited little or no inflammation at low (22cm(2)) or high (220cm(2)) nanoparticle surface area doses per animal, whereas equivalent surface area doses of the two nanoparticles with high HIC index values (0.88-0.96) induced neutrophil infiltration, elevation of pro-inflammatory cytokines and adverse histopathology findings. In summary, a HIC index is reported that provides a versatile, discriminatory, and widely available measure of nanoparticle surface hydrophobicity. The avoidance of high (HIC index>~0.8) surface hydrophobicity appears to be important for the design of safe nanomedicines for inhalation therapy.
Original languageEnglish
Pages (from-to)94-104
Number of pages11
JournalJournal of Controlled Release
Early online date19 Mar 2014
Publication statusPublished - 10 Jun 2014


  • Administration, Inhalation
  • Animals
  • Apoptosis
  • Biocompatible Materials
  • Bronchoalveolar Lavage Fluid
  • Cell Line
  • Chromatography, Liquid
  • Cytokines
  • Drug Carriers
  • Hydrophobic and Hydrophilic Interactions
  • Lipids
  • Lung
  • Male
  • Mice, Inbred BALB C
  • Nanoparticles
  • Particle Size
  • Pneumonia
  • Polystyrenes
  • Polyvinyls
  • Surface Properties
  • Journal Article
  • Research Support, Non-U.S. Gov't


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