title: Nanoparticle distribution during systemic inflammation is size-dependent and organ-specific.
abstract: This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Taipei 115, Taiwan. phsieh@ibms.sinica.edu.tw.
authors.forename: K-H
authors.initials: KH
authors.lastname: Chen
authors.forename: D J
authors.initials: DJ
authors.lastname: Lundy
authors.forename: E K-W
authors.initials: EK
authors.lastname: Toh
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Shih
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: H-C
authors.initials: HC
authors.lastname: Chang
authors.forename: J J
authors.initials: JJ
authors.lastname: Lai
authors.forename: P S
authors.initials: PS
authors.lastname: Stayton
authors.forename: A S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: P C-H
authors.initials: PC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D005456:Fluorescent Dyes