Publications (2)7.68 Total impact
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Article: Chitosan nanoparticles show rapid extrapulmonary tissue distribution and excretion with mild pulmonary inflammation to mice.
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ABSTRACT: Pulmonary delivery of nanoparticles (NP) conjugated with therapeutic agents has been considered recently for both lung disorders and systemic circulation. Hydrophobically modified glycol chitosan (HGC) NP have previously shown excellent deposition to the tumor site and non-destructive intracellular release. Here, we evaluated the kinetics and toxicity of HGC NP by intratracheal instillation to mice. HGC NP showed a positive charge and average hydrodynamic size was around 350 nm. The half-life of NP in the lung was determined as 131.97±50.51 h. NP showed rapid uptake into systemic circulation and excretion via urine which was peaked at 6h after instillation. Although HGC NP were distributed to several extrapulmonary organs, the levels were extremely low and transient. HGC NP induced transient neutrophilic pulmonary inflammation from 6h to day 3 after instillation. Expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and chemokine (MIP-1α) in lung showed an increase from 1h to 24h after instillation and recovered thereafter. Our findings suggest that HGC NP can be successful candidates for use as pulmonary delivery vehicles, owing to their excellent biocompatibility, transiency, and low pulmonary toxicity, and property of rapid elimination without accumulation.Toxicology Letters 11/2010; 199(2):144-52. · 3.23 Impact Factor -
Article: Size-dependent tissue kinetics of PEG-coated gold nanoparticles.
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ABSTRACT: Gold nanoparticles (AuNPs) can be used in various biomedical applications, however, very little is known about their size-dependent in vivo kinetics. Here, we performed a kinetic study in mice with different sizes of PEG-coated AuNPs. Small AuNPs (4 or 13nm) showed high levels in blood for 24h and were cleared by 7days, whereas large (100nm) AuNPs were completely cleared by 24h. All AuNPs in blood re-increased at 3months, which correlated with organ levels. Levels of small AuNPs were peaked at 7days in the liver and spleen and at 1month in the mesenteric lymph node, and remained high until 6months, with slow elimination. In contrast, large AuNPs were taken up rapidly ( approximately 30min) into the liver, spleen, and mesenteric lymph nodes with less elimination phase. TEM showed that AuNPs were entrapped in cytoplasmic vesicles and lysosomes of Kupffer cells and macrophages of spleen and mesenteric lymph node. Small AuNPs transiently activated CYP1A1 and 2B, phase I metabolic enzymes, in liver tissues from 24h to 7days, which mirrored with elevated gold levels in the liver. Large AuNPs did not affect the metabolic enzymes. Thus, propensity to accumulate in the reticuloendothelial organs and activation of phase I metabolic enzymes, suggest that extensive further studies are needed for practical in vivo applications.Toxicology and Applied Pharmacology 02/2010; 245(1):116-23. · 4.45 Impact Factor
