title: Quantitative assessment of nanoparticle surface hydrophobicity and its influence on pulmonary biocompatibility.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Jones
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Yanira
authors.initials: Y
authors.lastname: Riffo-Vasquez
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Domenico
authors.initials: D
authors.lastname: Spina
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Hoffman
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Morgan
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Aateka
authors.initials: A
authors.lastname: Patel
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Clive
authors.initials: C
authors.lastname: Page
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK. Electronic address: ben.forbes@kcl.ac.uk.
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, UK. Electronic address: lea_ann.dailey@kcl.ac.uk.
authors.forename: Lea Ann
authors.initials: LA
authors.lastname: Dailey
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry* / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D002853:Chromatography, Liquid / Q000379:methods*; D016207:Cytokines / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D011137:Polystyrenes / Q000633:toxicity; D011145:Polyvinyls / Q000633:toxicity; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D004337:Drug Carriers; D008055:Lipids; D011137:Polystyrenes; D011145:Polyvinyls; C013215:polyvinyl acetate
keywords: Hydrophobicity; Lipid nanocapsules; Nanomedicine; Nanotoxicology; Polystyrene; Pulmonary drug delivery